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Toxic Metals Data

Life Flow One
The Solution For Heart Disease

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HealthGate Documents

Record 1 from database: MEDLINE
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Title

Induction of p21 mediated by reactive oxygen species formed during the metabolism of aziridinylbenzoquinones by HCT116 cells.

Author

Qiu X; Forman HJ; Schönthal AH; Cadenas E

Address

Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA.

Source

J Biol Chem, 1996 Dec, 271:50, 31915-21

Abstract

Aziridinylbenzoquinones are a group of antitumor agents that elicit cytotoxicity by generating either alkylating intermediates or reactive oxygen species. The mechanism of toxicity may not always, however, involve profound damage of cellular constituents, but may involve a cytostatic effect through interference with the cell cycle. In this context, we have examined the induction of the cell cycle inhibitor p21 (WAF1, CIP1, or sdi1), whose overexpression suppresses the growth of various tumor cells, in human tumor cells metabolizing 3,6-diaziridinyl-1,4-benzoquinone (DZQ) and its C2,C5-substituted derivatives: 2,5-bis-(carboethoxyamino) (AZQ) and 2, 5-bis-2(-hydroxyethylamino) (BZQ). Both DZQ and AZQ were effectively activated by HCT116 human colonic carcinoma cells; the activation of the former involved largely a dicoumarol-sensitive activity, whereas that of the latter appeared to be accomplished primarily by one-electron transfer reductases. BZQ was not a substrate for the dicoumarol-sensitive enzyme in HCT116 cells. Cellular activation of the first two quinones was associated with formation of oxygen-centered radicals as detected by EPR in conjunction with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide. The redox transitions of DZQ involved hydroxyl radical formation and were strongly inhibited by catalase, whereas those of AZQ showed a strong superoxide anion component sensitive to superoxide dismutase. These signals were suppressed by N-acetylcysteine with concomitant production of a thiyl radical adduct. This suggests an effective electron transfer between the thiol and free radicals formed during the activation of these quinones. DZQ and AZQ induced significantly the expression of p21 in HCT116 cells, but a 10-fold higher concentration of AZQ was required to achieve the level of induction elicited by DZQ. BZQ had little effect on p21 expression. p21 induction at both mRNA and protein levels correlated with the inhibition of either cyclin-dependent kinase activity or cell proliferation. p21 induction elicited by the above quinones was inhibited by N-acetylcysteine, whereas the non-sulfur analog, N-acetylalanine, was without effect. Catalase and superoxide dismutase did not effect p21 induction by aziridinylbenzoquinones in HCT116 cells, thus suggesting that extracellular sources of oxygen radicals generated by plasma membrane reductases have no influence in the expression of this gene. Hydrogen peroxide, a product of quinone redox cycling, elicited an increase of p21 mRNA levels in HCT116 and K562 human chronic myelogenous leukemia cells. The latter lacks p53, one of the activators of p21 transcription, thus suggesting that p21 expression can be accomplished in a p53-independent manner in these cells. This study suggests that p21 induction is mediated by an increase in the cellular steady-state concentration of oxygen radicals and that the greater effectiveness in p21 induction by DZQ may be related to its efficient metabolism by NAD(P)H:quinone oxidoreductase activity in HCT116 cells.

Language of Publication

English

Unique Identifier

97112983

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MeSH Heading (Major)

Antineoplastic Agents|CH/*ME; Aziridines|*CH/ME; Benzoquinones|*CH/ME; Cyclins|*ME; Enzyme Inhibitors|*ME; Oxygen|*ME

MeSH Heading

Acetylcysteine|PD; Alanine|AA/PD; Cell Division|DE; Dicumarol|PD; Free Radicals|ME; Human; Hydrogen Peroxide|PD; NADP|ME; Oxidation-Reduction; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
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Title

Mechanism of cytosine arabinoside toxicity to the blast cells of acute myeloblastic leukemia: involvement of free radicals.

Author

Hu ZB; Yang GS; Li M; Miyamoto N; Minden MD; McCulloch EA

Address

Ontario Cancer Institute, Toronto, Canada.

Source

Leukemia, 1995 May, 9:5, 789-98

Abstract

Retinoic acid and hydrocortisone (HC) have been shown to regulate the drug sensitivity of the blast cells of acute myeloblastic leukemia (AML). We asked if the proto-oncogene bcl-2 played a role in this regulation. As target cells we used the continuous lines, OCI/AML-1, OCI/AML-2 or OCI/AML-5; expression of bcl-2 can be detected by Northern analysis of RNA from OCI/AML-2 or OCI/AML-5 cells; bcl-2 expression can be found in OCI/AML-1 cells only by using RT-PCR. Exposure of OCI/AML-2 or OCI/AML-5 cells to retinoic acid (all-trans retinoic acid, ATRA) led to a down-regulation of bcl-2 expression that was first seen after 2 h of exposure and was complete after a day. The down-regulation could be prevented by exposing the cells to ara-C either before or after ATRA; decrease in bcl-2 protein was moderate and only obvious after 36 h of ATRA treatment. Nuclear run-on experiments provided evidence that bcl-2 down-regulation was occurring at transcriptional and post-translational levels. Since bcl-2 is considered to have anti-oxidant activity, we tested the sensitivity of the three cell lines to H2O2; we found that OCI/AML-1, the line with very low bcl-2 expression, was a 100-fold more H2O2-sensitive than OCI/AML-2 or OCI/AML-5, where bcl-2 expression can be detected readily. We then asked if H2O2 sensitivity could be regulated. We found that exposure of cells to HC before H2O2 was protective while ATRA after peroxide treatment increased killing; this is the same pattern of regulation observed when AML blasts are exposed to HC before, or ATRA after ara-C. Finally, we asked whether N-acetylcysteine (NAC), a known radical scavenger would protect cells against ara-C killing. Significant protection was observed when NAC was given before drug, but not if given after drug. NAC protection against ara-C killing was seen for OCI/AML-1 and 2 cells, but not for OCI/AML-5 cells. We interpret the results as follows: ara-C kills cells in two ways: first, directly, by incorporation into DNA and chain termination; second, indirectly, by inducing the production of toxic radicals. Bcl-2 reduces the oxidant activity of such radicals, and is protective. ATRA regulates ara-C toxicity by its action on bcl-2. Left unexplained are the action of HC, which does not affect bcl-2 expression and the mechanism by which ara-C prevents down-regulation of bcl-2 by ATRA.

Language of Publication

English

Unique Identifier

95287643

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MeSH Heading (Major)

Cytarabine|*TO; Hydrogen Peroxide|ME/*TO; Leukemia, Myelocytic, Acute|*DT/ME/PA; Lymphocytes|*DE

MeSH Heading

Acetylcysteine|PD; Antioxidants|PD; Base Sequence; Blotting, Northern; Comparative Study; Down-Regulation (Physiology)|DE; Drug Interactions; Drug Screening Assays, Antitumor; Free Radicals|ME/TO; Gene Expression Regulation, Leukemic|DE; Human; Hydrocortisone|PD; Lymphocyte Transformation; Molecular Sequence Data; Polymerase Chain Reaction; Proto-Oncogene Proteins|GE/ME; Support, Non-U.S. Gov't; Transcription, Genetic|DE; Tretinoin|PD; Tumor Cells, Cultured|DE

Publication Type

JOURNAL ARTICLE

ISSN

0887-6924

Country of Publication

ENGLAND

Record 3 from database: MEDLINE
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Title

Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril.

Author

Ota Y; Kugiyama K; Sugiyama S; Ohgushi M; Matsumura T; Doi H; Ogata N; Oka H; Yasue H

Address

Division of Cardiology, Kumamoto University School of Medicine, Honjo, Kumamoto City, Japan.

Source

Atherosclerosis, 1997 Jun, 131:2, 195-202

Abstract

The aim of this study was to examine the effects of the water soluble component of cigarette smoke extract (CSE) on endothelium-dependent relaxation (EDR) of isolated rabbit aortas. The incubation with CSE was found to inhibit EDR in a dose-dependent manner. Co-incubation of the aortic strips with superoxide dismutase (SOD), N-acetylcysteine, glutathione or dimethyl sulfoxide (DMSO), free radical scavengers, attenuated the CSE-induced inhibition of the arterial relaxation. Co-incubation of the strips with captopril (3 mM), an angiotensin converting enzyme inhibitor, also attenuated CSE-induced impairment of vasorelaxation. In parallel experiments using cultured human endothelial cells, CSE suppressed endothelial release of NOx, stable metabolites of nitric oxide (NO). SOD, DMSO and captopril attenuated the suppression of NO production by CSE in association with reduction of free radicals, superoxide anions and hydroxyl radicals, in CSE solution. Neither lactate dehydrogenase release from the cultured endothelial cells nor cell death estimated by trypan blue exclusion test was found after the incubation of the cultured endothelial cells with CSE. The results indicate that free radicals in CSE induce the impairment of EDR, which may be partly due to suppression of NO production and is not due to non-specific cytotoxicity by CSE. Captopril attenuates CSE-induced endothelial dysfunction partly through scavenging free radicals.

Language of Publication

English

Unique Identifier

97342575

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MeSH Heading (Major)

Angiotensin-Converting Enzyme Inhibitors|*PD; Captopril|*PD; Endothelium, Vascular|DE/*PH; Muscle, Smooth, Vascular|DE/*PH; Smoking|*AE; Tobacco|*; Vasodilation|*

MeSH Heading

Acetylcysteine|PD; Animal; Aorta, Thoracic|DE/PH; Cell Division; Cells, Cultured; Comparative Study; Free Radical Scavengers|PD; Free Radicals; Glutathione|PD; Human; Male; Nitric Oxide|BI; Rabbits; Superoxide Dismutase|PD; Support, Non-U.S. Gov't; Umbilical Veins

Publication Type

JOURNAL ARTICLE

ISSN

0021-9150

Country of Publication

IRELAND

Record 4 from database: MEDLINE
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Title

Effect of N-acetylcysteïne on Photofrin-induced skin photosensitivity in patients.

Author

Baas P; van Mansom I; van Tinteren H; Stewart FA; van Zandwijk N

Address

Division of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.

Source

Lasers Surg Med, 1995, 16:4, 359-67

Abstract

BACKGROUND AND OBJECTIVE: One of the major side effects of photodynamic therapy (PDT) employing Photofrin as the sensitizer is enhanced photosensitivity of the skin. The basic mechanism in PDT damage is believed to be the formation of singlet oxygen and radical species. N-acetylcysteïne (NAC) increases glutathione levels and is known to prevent pathology elicited by radicals and reactive species. STUDY DESIGN/MATERIALS AND METHODS: NAC was tested in a randomized, open label study for its protective effect on skin photosensitivity. Twenty-seven patients treated with PDT for central obstructive lung cancer or esophageal cancer received either "early" or "delayed" NAC, starting 5 or 10 days after Photofrin, in a dose of 3 x 600 mg per day for 5 days. Light, obtained from a halogen lamp (fluence rate 200 mW.cm-2) was used to illuminate skin patches of 2.5 cm2 on the back (10, 25, and 50 J.cm-2). Skin response was measured by using a visual scoring system and by measuring the redness using a reflectance meter. RESULTS: Skin responses varied from no changes at 10 J.cm-2 to redness with edema at energies of 50 J.cm-2. In the absence of edema, measurements with the reflectance meter appeared to be more sensitive than visual scoring. CONCLUSION: In a limited number of patients, there was a trend for decreased sensitivity after NAC, but statistical analysis failed to show any significant protective effect of this short course of NAC.

Language of Publication

English

Unique Identifier

95379406

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MeSH Heading (Major)

Acetylcysteine|AD/*TU; Dihematoporphyrin Ether|AD/*AE; Photosensitivity Disorders|CI/*PC; Skin|*DE/ME/*RE

MeSH Heading

Adult; Aged; Aged, 80 and over; Edema|CI/PC; Erythema|CI/PC; Esophageal Neoplasms|RT; Female; Follow-Up Studies; Free Radicals|AE; Glutathione|ME; Human; Lung Neoplasms|DT; Male; Middle Age; Photochemotherapy|AE; Reactive Oxygen Species|AE; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0196-8092

Country of Publication

UNITED STATES

Record 5 from database: MEDLINE
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Title

L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as precursors of intracellular glutathione in human peritoneal mesothelial cells.

Author

Breborowicz A; Patrikarea A; Martis L; Oreopoulos DG

Address

Department of Pathophysiology, Medical School, Poznan, Poland.

Source

Blood Purif, 1996, 14:1, 1-7

Abstract

L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as substrates for intracellular glutathione in human peritoneal mesothelial cells were tested. Both substances at concentrations of 0.01 mM and higher augmented the level of glutathione in mesothelial cells. L-2-Oxothiazolidine-4-carboxylate had a milder but more stable effect than N-acetylcysteine. Cells with increased concentrations of the intracellular glutathione were more resistant to injury by free radicals. When used at higher concentrations (> 1 mM), both substances became cytostatic to mesothelial cells as evidenced by growth inhibition.

Language of Publication

English

Unique Identifier

96351938

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MeSH Heading (Major)

Acetylcysteine|*PD; Free Radical Scavengers|*PD; Glutathione|*ME; Peritoneum|CY/*DE/ME; Protein Precursors|*ME; Thiazoles|*PD

MeSH Heading

Cells, Cultured; Epithelium|CY/DE/ME; Free Radicals; Human

Publication Type

JOURNAL ARTICLE

ISSN

0253-5068

Country of Publication

SWITZERLAND

Record 6 from database: MEDLINE
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Title

Endogenous intracellular glutathionyl radicals are generated in neuroblastoma cells under hydrogen peroxide oxidative stress.

Author

Kwak HS; Yim HS; Chock PB; Yim MB

Address

Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Source

Proc Natl Acad Sci U S A, 1995 May, 92:10, 4582-6

Abstract

We report the detection of endogenous intracellular glutathionyl (GS.) radicals in the intact neuroblastoma cell line NCB-20 under oxidative stress. Spin-trapping and electron paramagnetic resonance (EPR) spectroscopic methods were used for monitoring the radicals. The cells incubated with the spin trap 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) were challenged with H2O2 generated by the enzymic reaction of glucose/glucose oxidase. These cells exhibit the EPR spectrum of the GS. radical adduct of DMPO (DMPO-.SG) without exogenous reduced glutathione (GSH). The identity of this radical adduct was confirmed by observing hyperfine coupling constants identical to previously reported values in in vitro studies, which utilized known enzymic reactions, such as horseradish peroxidase and Cu/Zn superoxide dismutase, with GSH and H2O2 as substrates. The formation of the GS. radicals required viable cells and continuous biosynthesis of GSH. No significant effect on the resonance amplitude by the addition of a membrane-impermeable paramagnetic broadening agent indicated that these radicals were located inside the intact cell. N-Acetyl-L-cysteine (NAC)-treated cells produced NAC-derived free radicals (NAC.) in place of GS. radicals. The time course studies showed that DMPO-.SG formation exhibited a large increase in its concentration after a lag period, whereas DMPO-NAC. formation from NAC-treated cells did not show this sudden increase. These results were discussed in terms of the limit of antioxidant enzyme defenses in cells and the potential role of the GS. radical burst in activation of the transcription nuclear factor NF-kappa B in response to oxidative stress.

Language of Publication

English

Unique Identifier

95273407

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MeSH Heading (Major)

Free Radicals|*ME; Glutathione|*ME; Hydrogen Peroxide|*PD; Neuroblastoma|*ME

MeSH Heading

Acetylcysteine|PD; Cell Line; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Glucose; Glucose Oxidase; Horseradish Peroxidase|PD; Human; Kinetics; NF-kappa B|ME; Oxidative Stress; Spin Labels; Superoxide Dismutase|PD; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

Record 7 from database: MEDLINE
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Title

The effects of intravenous antioxidants in patients with septic shock.

Author

Galley HF; Howdle PD; Walker BE; Webster NR

Address

Academic Unit of Anaesthesia & Intensive Care, University of Aberdeen, UK. h.f.galley@abdn.ac.uk

Source

Free Radic Biol Med, 1997, 23:5, 768-74

Abstract

Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. Basal vitamin C was low and redox-reactive iron was elevated in all patients. In the 16 patients receiving antioxidants, vitamin C increased (p = .0002) but total antioxidant capacity was unaffected. Lipid peroxides were elevated in all patients but did not increase further in the patients receiving antioxidants. Plasma total nitrite also increased (p = .007) in the antioxidant group. Heart rate increased in patients receiving antioxidants at 60 min (p = .018) and 120 min (p = .004). Cardiac index also increased at 60 min (p = .007) and 120 min (p = .05). Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.

Language of Publication

English

Unique Identifier

97440995

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MeSH Heading (Major)

Antioxidants|AD/AN/*TU; Shock, Septic|BL/*DT/PP

MeSH Heading

Acetylcysteine|AD/TU; Adult; Aged; Aged, 80 and over; Ascorbic Acid|AD/BL/TU; Drug Therapy, Combination; Free Radicals|ME; Hemodynamics|DE; Human; Injections, Intravenous; Lipid Peroxides|BL; Male; Middle Age; Nitrites|BL; Oxidation-Reduction; Support, Non-U.S. Gov't; Vitamin E|AD/TU

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0891-5849

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
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Title

Inhibitory effect of estrogens on the oxidative hemolysis induced by 2-amidinopropane hydrochloride, a free radical generator.

Author

Vibert Li JL; Okada S

Address

Etypharm, Division MÆedicale, Saint Cloud, France.

Source

Acta Med Okayama, 1996 Jun, 50:3, 125-30

Abstract

We investigated the effect of estrogens, 17 beta-estradiol, estradiol-3-benzoate and estrone, on 2-amidinopropane hydrochloride (AAPH)-provoked, free radical-dependent hemolysis in vitro. Incubation experiment was performed by mixing AAPH (400 mM) and washed human erythrocyte suspension with or without various sex hormones and radical scavengers. After 170 min of incubation, 50% hemolysis was detected in the control group (incubation without sex hormones or radical scavengers), whereas after the addition of estrogens (5 mM), hemolysis was nearly completely inhibited until 180 min of incubation. It was found that the inhibitory activities of estrogens on oxidative hemolysis were stronger than that of alpha-tocopherol and had nearly identical to that of N-acetyl-L-cysteine. Testosterone had no inhibitory effects. The elevation of thiobarbituric acid-reactive substances, a marker for lipid peroxidation, was also inhibited by estrogens. These results add further evidence that estrogens are strong radical scavengers in humans.

Language of Publication

English

Unique Identifier

96399340

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MeSH Heading (Major)

Amidines|*PD; Estradiol|*PD; Estrone|*PD; Hemolysis|*DE

MeSH Heading

Acetylcysteine|PD; Antioxidants|PD; Cells, Cultured; Erythrocytes|DE; Free Radicals|ME; Human; Oxidation-Reduction|DE; Thiobarbituric Acid Reactive Substances|ME; Vitamin E|PD

Publication Type

JOURNAL ARTICLE

ISSN

0386-300X

Country of Publication

JAPAN

Record 9 from database: MEDLINE
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Title

Effects of oxidants and antioxidants on nuclear factor kappa B activation in three different cell lines: evidence against a universal hypothesis involving oxygen radicals.

Author

Brennan P; ONeill LA

Address

Biochemistry Department, Trinity College, Dublin, Ireland.

Source

Biochim Biophys Acta, 1995 Jan, 1260:2, 167-75

Abstract

A model for NF kappa B activation involving reactive oxygen intermediates has recently been proposed. We have explored this model in three cell lines, Jurkat T cells, EL4.NOB-1 T cells and KB epidermal cells using hydrogen peroxide and two physiological activators of NF kappa B, interleukin-1 (IL1) and tumor necrosis factor (TNF) as stimuli. In agreement with earlier studies hydrogen peroxide activated NF kappa B in Jurkat, although only at much higher concentrations (10 mM) than those previously reported. However, hydrogen peroxide failed to activate in the two other cell lines under a range of conditions. Similarly, N-acetylcysteine only proved inhibitory in hydrogen peroxide and TNF treated Jurkat and failed to inhibit IL1 and TNF-activated NF kappa B in EL4.NOB-1 and KB cells respectively. N-Acetylcysteine inhibited IL1-induced interleukin-2 in EL4, however, demonstrating that N-acetylcysteine was biologically active. These results suggest that the reactive oxygen model of NF kappa B activation may be cell-type restricted. In contrast to the results with N-acetylcysteine, the antioxidant and metal chelator, pyrolidine dithiocarbamate (PDTC) inhibited NF kappa B activation, although these effects may be unrelated to any antioxidant properties. PDTC also inhibited IL1-induced interleukin-2. Finally, studies with the pro-oxidant diamide showed that this could not activate NF kappa B in any of the cells and in contrast proved inhibitory. The results from this study therefore suggest that the reactive oxygen model of NF kappa B activation may be restricted to certain cell types and that the presence of such a system is not required for the activation of NF kappa B by IL1 and TNF.

Language of Publication

English

Unique Identifier

95143273

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MeSH Heading (Major)

Hydrogen Peroxide|*PD; Interleukin-1|*PD; NF-kappa B|*ME; Oxygen|*ME; Tumor Necrosis Factor|*PD

MeSH Heading

Acetylcysteine|PD; Animal; Base Sequence; Cell Line; Comparative Study; Free Radicals; Human; Mice; Molecular Sequence Data; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0006-3002

Country of Publication

NETHERLANDS

Record 10 from database: MEDLINE
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Title

Effect of antioxidants on radical intensity and cytotoxic activity of eugenol.

Author

Satoh K; Ida Y; Sakagami H; Tanaka T; Fujisawa S

Address

Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.

Source

Anticancer Res, 1998 May-Jun, 18:3A, 1549-52

Abstract

The effect of antioxidants on the radical intensity of 2-methoxy-4-(2-propenyl)phenol (eugenol) was investigated, using ESR spectroscopy. Eugenol produced radicals in alkaline solutions, with an optimum pH of 9.5. The intensity of eugenol radical was a positive function of its concentration, reaching a plateau level at 100 mM. The eugenol radical was rapidly diminished under alkaline conditions. Water-soluble antioxidants, such as cysteine, N-acetyl-L-cysteine, glutathione and sodium ascorbate, completely scavenged the eugenol radical. Gallic acid at lower doses significantly, but not completely, scavenged the eugenol radical. Among water-insoluble antioxidants, terpenes (beta-carotene, retinol, lycopene) effectively scavenged the eugenol radical, whereas phenolic compounds (alpha-tocopherol, Trolox) were inactive. Millimolar concentrations of eugenol were cytotoxic against human salivary gland and oral squamous carcinoma cell lines. Addition of sodium ascorbate or beta-carotene reproducibly reduced the cytotoxic activity of eugenol. The applicability of the antioxidants in dentistry was discussed.

Language of Publication

English

Unique Identifier

98338086

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MeSH Heading (Major)

Antioxidants|*PD; Cell Survival|*DE; Eugenol|*CH/*TO; Vitamins|*PD

MeSH Heading

Acetylcysteine|PD; Ascorbic Acid|PD; Beta Carotene|PD; Carcinoma, Squamous Cell; Carotene|PD; Chromans|PD; Cysteine|PD; Electron Spin Resonance Spectroscopy; Free Radicals; Gallic Acid|PD; Glutathione|PD; Human; Hydrogen-Ion Concentration; Kinetics; Mouth Neoplasms; Salivary Gland Neoplasms; Tumor Cells, Cultured; Vitamin A|PD; Vitamin E|PD

Publication Type

JOURNAL ARTICLE

ISSN

0250-7005

Country of Publication

GREECE

CAS Registry/EC Number

0 (Antioxidants); 0 (Chromans); 0 (Free Radicals); 0 (Vitamins); 11103-57-4 (Vitamin A); 1406-18-4 (Vitamin E); 149-91-7 (Gallic Acid); 36-88-4 (Carotene); 4371-52-2 (Cysteine); 50-81-7 (Ascorbic Acid); 502-65-8 (lycopene); 56305-04-5 (Trolox C); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione); 7235-40-7 (Beta Carotene); 97-53-0 (Eugenol)

Record 11 from database: MEDLINE
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Title

Effect of cysteine, N-acetyl-L-cysteine and glutathione on cytotoxic activity of antioxidants.

Author

Satoh K; Sakagami H

Address

Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.

Source

Anticancer Res, 1997 May, 17:3C, 2175-9

Abstract

The effect of twenty amino acids on the radical intensity of four antioxidants (sodium L-ascorbate, sodium 5,6-benzylidene-L-ascorbate, gallic acid, caffeic acid) was investigated, using ESR spectroscopy. Methionine and methional did not significantly affect the radical intensity of these antioxidants. Methionine sulfoxide slightly enhanced the radical intensity of sodium ascorbate and sodium 5,6-benzylidene-L-ascorbate, but did not that of gallic acid and caffeic acid. Cysteine, N-acetyl cysteine and glutathione significantly reduced the radical intensity and cytotoxic activity of these antioxidants except for sodium 5,6-benzylidene-L-ascorbate. The other amino acids were inactive. The present study further supports that these antioxidants induce cytotoxicity via their pro-oxidant action.

Language of Publication

English

Unique Identifier

97359767

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MeSH Heading (Major)

Acetylcysteine|*PD; Amino Acids|*PD; Antioxidants|ME/*TO; Cell Survival|*DE; Cysteine|*PD; Glutathione|*PD

MeSH Heading

Amino Acids, Essential|PD; Antineoplastic Agents|ME/TO; Ascorbic Acid|AA/TO; Benzylidene Compounds|TO; Caffeic Acids|TO; Electron Spin Resonance Spectroscopy; Free Radicals|ME; Gallic Acid|TO; Human; HL-60 Cells|DE; Kinetics

Publication Type

JOURNAL ARTICLE

ISSN

0250-7005

Country of Publication

GREECE

Record 12 from database: MEDLINE
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Title

Abnormalities of antioxidant metabolism in a case of Friedreich's disease.

Author

Helveston W; Cibula JE; Hurd R; Uthman BM; Wilder BJ

Address

Department of Neurology, University of Florida, Gainesville, USA.

Source

Clin Neuropharmacol, 1996 Jun, 19:3, 271-5

Abstract

We report a patient with Friedreich's disease (FD) who exhibited abnormalities of antioxidant metabolism, including decreased levels of glutathione peroxidase, glutathione reductase, and selenium, and an increased lipid peroxide index. These abnormalities became normal after treatment with N-acetylcysteine, selenium, and low-dose vitamin E therapy. Treatment was associated with a decreased rate of clinical decline. FD is a neurodegenerative disorder that may be related to disturbed antioxidant metabolism; the disorder may be treatable with antioxidant compounds.

Language of Publication

English

Unique Identifier

96338440

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MeSH Heading (Major)

Acetylcysteine|*TU; Antioxidants|ME/*TU; Myoclonus|*BL/*DT

MeSH Heading

Adult; Case Report; Female; Free Radicals|ME; Glutathione Peroxidase|BL; Glutathione Reductase|BL; Human; Lipid Peroxides|BL; Selenium|TU; Vitamin E|TU

Publication Type

JOURNAL ARTICLE

ISSN

0362-5664

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
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Title

Oxygen radical release by neutrophils of HIV-infected patients.

Author

Jarstrand C; Akerlund B

Address

Department for Clinical Microbiology, Huddinge University Hospital, Sweden.

Source

Chem Biol Interact, 1994 Jun, 91:2-3, 141-6

Abstract

Neutrophils from asymptomatic HIV-infected patients have an increased Nitroblue tetrazolium (NBT) reduction, that is an increased production of oxygen radicals. Plasma from these patients can activate normal neutrophils to an increased NBT-reduction and the neutrophil activating factor thus seems to be mainly plasma bound. Further, the patients also have increased levels of plasma malondialdehyde and thus an increased lipid peroxidation. Plasma cysteine levels are low, a sign of increased consumption of antioxidants. Treatment of the asymptomatic HIV-infected patients with N-acetylcysteine corrected the plasma cysteine levels and had some beneficial effects, but did not inhibit the increased radical production by the neutrophils.

Language of Publication

English

Unique Identifier

94251840

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MeSH Heading (Major)

Acetylcysteine|*TU; HIV Infections|*BL/DT; Neutrophils|*ME; Superoxides|*BL

MeSH Heading

Acquired Immunodeficiency Syndrome|BL; Adult; AIDS-Related Complex|BL; Cysteine|BL; Female; Free Radicals; Human; Male; Oxidation-Reduction; Randomized Controlled Trials

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0009-2797

Country of Publication

IRELAND

Record 14 from database: MEDLINE
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Title

Role of oxygen radicals in 12-O-tetradecanoylphorbol-13-acetate-induced squamous differentiation of cultured normal human bronchial epithelial cells.

Author

Gabrielson EW; Rosen GM; Grafstrom RC; Strauss KE; Miyashita M; Harris CC

Address

Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland 20892.

Source

Cancer Res, 1988 Feb 15, 48:4, 822-5

Abstract

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits growth and induces terminal squamous differentiation of normal human bronchial cells when added to the culture media [J. C. Willey, A. J. Saladino, C. Ozanne, J. F. Lechner, and C. C. Harris, Carcinogenesis (lond.), 5: 209-215, 1984]. We have investigated the possibility of oxygen free radicals being involved as intermediates in this process. Electron paramagnetic resonance measurements using the spin-trapping agent 5,5-dimethyl-1-pyrroline-1-oxide failed to detect oxygen free radicals in bronchial epithelial cells exposed to TPA, although oxy radicals were detected in bronchial epithelial cells after a nontoxic exposure to menadione, and in human neutrophils after exposure to TPA. Addition to the culture media of free radical scavenger, i.e., reduced glutathione, N-acetylcysteine, D-alpha-tocopherol, copper (II) (3,5-diisopropylsalicyclic acid)2, or the combination of superoxide dismutase and catalase did not affect the dose-dependent growth inhibition of TPA on the bronchial epithelial cells. Moreover, exposure of the bronchial epithelial cells to TPA did not result in increased DNA single strand breaks measured by alkaline elution, as would be expected with a free radical mediated mechanism. Thus, our results argue against the importance of oxygen free radicals in the inhibition of growth and the induction of squamous differentiation by TPA in normal human bronchial epithelial cells.

Language of Publication

English

Unique Identifier

88109349

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MeSH Heading (Major)

Bronchi|DE/*PA; Cell Survival|*DE; Tetradecanoylphorbol Acetate|*TO

MeSH Heading

Acetylcysteine|PD; Antineoplastic Agents|PD; Catalase|PD; DNA Damage; Electron Spin Resonance Spectroscopy; Epithelium|CY/DE; Free Radicals; Glutathione|PD; Human; Kinetics; Salicylic Acids|PD; Superoxide Dismutase|PD; Vitamin E|PD

Publication Type

JOURNAL ARTICLE

ISSN

0008-5472

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Antineoplastic Agents); 0 (Free Radicals); 0 (Salicylic Acids); 1406-18-4 (Vitamin E); 16561-29-8 (Tetradecanoylphorbol Acetate); 21246-18-4 (copper bis(3,5-diisopropylsalicylate)); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione)

Record 15 from database: MEDLINE
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Title

The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin in multidrug resistant and sensitive human ovarian cancer cells.

Author

Cervantes A; Pinedo HM; Lankelma J; Schuurhuis GJ

Address

Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.

Source

Cancer Lett, 1988 Aug 15, 41:2, 169-77

Abstract

The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin (Dox) was studied in a Dox sensitive human ovarian cancer cell line (A2780) and its multidrug resistant counterpart (2780AD) using reactive oxygen scavengers. In both cell lines, a significant inhibition of Dox toxicity was found after treatment with the hydroxyl radical scavengers, N-acetylcysteine, sodium benzoate and dimethyl sulfoxide, but not with mannitol. The protection was similar in sensitive and resistant cells: 13-39% less growth inhibition was found at Dox concentrations of 0.2 and 0.5 microM for A2780 as well as at 20 and 50 microM for 2780AD. This protection was not due to effects of the scavengers on Dox accumulation, as shown by uptake experiments with radio-labelled Dox. The superoxide anion free radical scavenger ascorbic acid or the enzyme superoxide dismutase as well as the hydrogen peroxide scavenger catalase did not protect cells against Dox-induced cell growth inhibition. Preloading the cells with the enzymes, a treatment which resulted in a two to nine-fold increase in their cellular contents, was not effective either. It is concluded that hydroxyl radicals, but not superoxide anion or hydrogen peroxide likely play a role in the antitumor activity of Dox in sensitive and resistant human ovarian cancer cells.

Language of Publication

English

Unique Identifier

88294969

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MeSH Heading (Major)

Doxorubicin|*PD; Oxygen|*ME; Tumor Cells, Cultured|*DE/ME

MeSH Heading

Acetylcysteine|PD; Ascorbic Acid|PD; Benzoates|PD; Catalase|PD; Cell Division|DE; Cell Survival|DE; Drug Resistance; Female; Free Radicals; Human; Hydroxides|ME; Kinetics; Mannitol|PD; Ovarian Neoplasms; Superoxide Dismutase|PD; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0304-3835

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Benzoates); 0 (Free Radicals); 0 (Hydroxides); 23214-92-8 (Doxorubicin); 3352-57-6 (Hydroxyl Radical); 50-81-7 (Ascorbic Acid); 616-91-1 (Acetylcysteine); 65-85-0 (benzoic acid); 69-65-8 (Mannitol); 7782-44-7 (Oxygen)

Record 16 from database: MEDLINE
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Title

Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: modulation by N-acetylcysteine treatment in vivo.

Author

Bergstrand H; Björnson A; Eklund A; Hernbrand R; Larsson K; Linden M; Nilsson A

Address

Source

J Free Radic Biol Med, 1986, 2:2, 119-27

Abstract

Bronchoalveolar lavage (BAL) was performed on nine healthy nonsmoking subjects and on 11 healthy smokers; in the last mentioned group lavage was performed before and after eight weeks treatment with N-acetylcysteine (NAC; 200 mg t.i.d.). The BAL cells were cultured for 2 h or overnight. Adherent cells were examined for their capacity to generate superoxide radicals (determined by superoxide dismutase (SOD)-inhibitable cytochrome C-reduction) at stimulation with phorbol 12-myristate 13-acetate (PMA), serum-treated zymosan (STZ), the calcium ionophore A23187, or the chemotactic tripeptide formyl-methionylleucylphenylalanine (FMLP). Cells from nonsmokers responded with a very low degree of O(2)-generation to any of the stimuli employed whether cultured for 2 h or overnight. Cells from smokers also responded with low O(2)-generation after 2 h of culture. However, cells from smokers cultured overnight responded with marked O(2)-generation to PMA and STZ but the responses to FMLP and A23187 were low. NAC-treatment of the smokers resulted in a reduced degree of both PMA- and STZ-induced O(2)-generation in five individuals. In two other subjects, PMA-induced (but not STZ-induced) O(2)-generation was reduced. Two individuals showed increased O(2)-generation to PMA- and to STZ-stimulation after NAC-treatment. Mean values of O(2)-generation induced by A23187 or by FMLP were significantly reduced for cells harvested after NAC-treatment. Mean values for PMA-induced O(2)-generation also tended to be reduced by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

87139037

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MeSH Heading (Major)

Acetylcysteine|*PD; Macrophages|*ME; Smoking|*; Superoxides|*ME

MeSH Heading

Free Radicals; Human; In Vitro; Pulmonary Alveoli|CY; Spirometry

Publication Type

JOURNAL ARTICLE

ISSN

0748-5514

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 11062-77-4 (Superoxides); 616-91-1 (Acetylcysteine)

Record 17 from database: MEDLINE
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Title

Lung protection by a thiol-containing antioxidant: N-acetylcysteine.

Author

Moldéus P; Cotgreave IA; Berggren M

Address

Source

Respiration, 1986, 50 Suppl 1:, 31-42

Abstract

N-acetylcysteine (NAC) is a thiol-containing compound which nonenzymatically interacts and detoxifies reactive electrophiles and free radicals. NAC was shown to effectively protect human bronchial fibroblasts against the toxic effects of tobacco smoke condensates and the isolated perfused lung against the glutathione (GSH)-depleting effect of tobacco smoke. NAC was also shown to reduce the reactive oxygen intermediate hydrogen peroxide (H2O2) and protect against the toxic effects of H2O2. In vivo studies, however, demonstrated that NAC when administered orally has very low bioavailability due to rapid metabolism to GSH among other metabolites. Thus, even though NAC is very effective in protecting cells of different origins from the toxicity of reactive components in tobacco smoke and reactive oxygen species, a direct scavenging effect by NAC in vivo, particularly when administered orally, does not seem likely. The bioavailability of NAC itself is very low when given this route. A more relevant mechanism in vivo for any protective effect NAC may exert against toxic species may be due to NAC acting as a precursor of GSH and facilitating its biosynthesis. GSH will then serve as the protective agent and detoxify reactive species both enzymatically and nonenzymatically.

Language of Publication

English

Unique Identifier

87119435

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MeSH Heading (Major)

Acetylcysteine|*PD; Antioxidants|*PD; Lung|*DE/ME; Smoking|*

MeSH Heading

Animal; Biological Availability; Free Radicals; Glutathione|PH; Human; Lung Diseases, Obstructive|PC; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0025-7931

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Antioxidants); 0 (Free Radicals); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione)

Record 18 from database: MEDLINE
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Title

Effects of antioxidants on oxidant-induced sister chromatid exchange formation.

Author

Weitberg AB; Weitzman SA; Clark EP; Stossel TP

Address

Source

J Clin Invest, 1985 Jun, 75:6, 1835-41

Abstract

Stimulated human phagocytes produce sister chromatid exchanges in cultured mammalian cells by a mechanism involving oxygen metabolites. Experiments were designed to determine whether antioxidants inhibit this process. Superoxide dismutase, catalase, and hydroxyl radical scavengers (benzoate, mannitol) protected target Chinese hamster ovary cells from phagocyte-induced sister chromatid exchanges, implicating the involvement of hydroxyl radicals in this chromosomal damage. N-acetylcysteine and beta-carotene were also protective. alpha-Tocopherol (greater than 5 microM) protected target cells exposed to phagocytes but not to enzymatically generated oxidants when the vitamin was added just before the source of oxygen radicals, suggesting, as reported by others, that the principal action of tocopherol in this setting was to inhibit the release of oxidants from phagocytes. On the other hand, cultivation of target cells with supplemental tocopherol protected them from the toxic effects of the enzymatic oxidant-producing system, indicating a role for membrane-associated free radicals in the mechanism of sister chromatid exchange induction. Low concentrations of sodium selenite (0.1-1.0 microM) protected the target cells. However, higher concentrations (10 microM) of selenite had no effect on oxidant-induced sister chromatid exchange formation, and 0.1 mM selenite increased the number of exchanges. Sodium selenite concentrations of 0.1 mM also decreased the intracellular glutathione concentration of target cells during an oxidant stress, and reducing target cell glutathione concentrations with buthionine sulfoximine increased their sensitivity to oxygen-related chromosomal damage. Therefore, the potentiation of oxygen radical-induced chromosomal damage observed with high concentrations of selenite may result from a decrease in the thiol antioxidant defense systems within the cell. The findings suggest that the hydroxyl radical has an important role in the production of phagocyte-induced cytogenetic injury, membrane-derived intermediates may be involved, depletion of intracellular glutathione renders cells more susceptible to this injury, and supplementation of target cells with antioxidants can protect them from oxygen radical-generated chromosomal injury.

Language of Publication

English

Unique Identifier

85234902

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MeSH Heading (Major)

Oxygen|AI/*TO; Sister Chromatid Exchange|*DE

MeSH Heading

Acetylcysteine|PD; Animal; Benzoates|PD; Carotene|PD; Catalase|ME; Cricetulus; Female; Free Radicals; Glutathione|ME; Hamsters; Human; Mannitol|PD; Ovary; Phagocytes|PH; Selenium|PD; Superoxide Dismutase|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vitamin E|PD; Xanthine Oxidase|DU

Publication Type

JOURNAL ARTICLE

ISSN

0021-9738

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.1.3.22 (Xanthine Oxidase); EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Benzoates); 0 (Free Radicals); 1406-18-4 (Vitamin E); 36-88-4 (Carotene); 616-91-1 (Acetylcysteine); 65-85-0 (benzoic acid); 69-65-8 (Mannitol); 70-18-8 (Glutathione); 7235-40-7 (Beta Carotene); 7782-44-7 (Oxygen); 7782-49-2 (Selenium); 7783-00-8 (selenious acid)

Record 19 from database: MEDLINE
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Title

The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action.

Author

Zimmerman RJ; Marafino BJ Jr; Chan A; Landre P; Winkelhake JL

Address

Department of Pharmacology, CETUS Corporation, Emeryville, CA 94608.

Source

J Immunol, 1989 Feb 15, 142:4, 1405-9

Abstract

The intracellular glutathione levels of two human tumor lines and seven murine tumor lines were determined in order to investigate the role of oxidant injury in tumor cell sensitivity to human rTNF (rhTNF). Correlations were found between high intracellular glutathione levels and in vivo tumor resistance to rhTNF, and on the other hand, low glutathione levels and rhTNF sensitivity. The transplantable murine fibrosarcoma, Meth A, a TNF-sensitive line in vivo, was less sensitive to rhTNF and host toxicity was reduced when the hosts were pretreated with uric acid, a major reactive oxygen scavenger in humans and certain other primates. Conversely, pretreatment of the tumor-bearing hosts with DL-buthionine-(S,R)-sulfoximine, an inhibitor of GSH biosynthesis, resulted in an increased sensitivity of Meth A to rhTNF. This effect was not limited to tumor-bearing mice, as rats pretreated with diethyl maleate, a compound which irreversibly binds glutathione, were more sensitive to rhTNF toxicity than control rats. On the other hand, pretreatment with N-acetyl cysteine, an oxidant scavenger, reduced the toxicity of rhTNF treatment in rats. The data are consistent with the hypothesis that tumor cell sensitivity to rhTNF in vivo is dependent on its capacity to buffer oxidative attack. In addition, host toxicity is also related to the production of reactive oxygen species. Activated effector cells such as granulocytes and macrophages are hypothesized to produce most of this damage by their respiratory burst and oxidant release, although the direct action of rhTNF may also contribute to oxidative injury in vivo.

Language of Publication

English

Unique Identifier

89124387

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MeSH Heading (Major)

Neoplasms, Experimental|*ME/PA/TH; Oxygen|*TO; Recombinant Proteins|*AD; Tumor Necrosis Factor|*AD

MeSH Heading

Acetylcysteine|AD; Animal; Female; Free Radicals; Glutathione|ME; Human; Lipid Peroxides|TO; Maleates|AD; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Rats; Rats, Inbred Strains

Publication Type

JOURNAL ARTICLE

ISSN

0022-1767

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 0 (Lipid Peroxides); 0 (Maleates); 0 (Recombinant Proteins); 0 (Tumor Necrosis Factor); 141-05-9 (diethyl maleate); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione); 7782-44-7 (Oxygen)

Record 20 from database: MEDLINE
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Title

Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages.

Author

Drost E; Lannan S; Bridgeman MM; Brown D; Selby C; Donaldson K; MacNee W

Address

Dept of Medicine (RIE), Rayne Laboratory, City Hospital, Edinburgh, UK.

Source

Eur Respir J, 1991 Jun, 4:6, 723-9

Abstract

N-acetylcysteine (NAC) is rapidly de-acetylated in vivo to cysteine (CYSH), a precursor of glutathione (GSH) which is an antioxidant in cells and body fluids. We investigated the effect of oral administration of N-acetyl cysteine for 5 days on the spontaneous and stimulated generation of hydrogen peroxide (H2O2) and superoxide anion (O2-) from human and rat phagocytic leucocytes. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) in control rats and rats given NAC in their drinking water. Neutrophils (PMNL) were harvested from whole blood in normal nonsmoking volunteers before and after NAC was given by mouth. The stimulated release of H2O2 and O2 from both rat AM and human PMN was not changed by administration of NAC. However, a small but significant increase was observed in both the spontaneous generation of O2- from rat AM and the spontaneous generation of H2O2 from human PMNL. Administration of NAC significantly increased cysteine levels in human plasma and rat BAL, but the levels in human PMNL and rat AM after NAC did not differ from control levels. GSH levels were not altered significantly by NAC.

Language of Publication

English

Unique Identifier

91364851

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MeSH Heading (Major)

Acetylcysteine|*PD; Macrophages|*DE/ME; Neutrophils|*DE/ME; Oxygen|*ME; Pulmonary Alveoli|*CY

MeSH Heading

Administration, Oral; Adult; Animal; Bronchoalveolar Lavage Fluid|CY; Cysteine|ME; Free Radicals; Glutathione|ME; Human; Rats; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0903-1936

Country of Publication

DENMARK

CAS Registry/EC Number

0 (Free Radicals); 4371-52-2 (Cysteine); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione); 7782-44-7 (Oxygen)

Record 21 from database: MEDLINE
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Title

Potential of N-acetylcysteine as treatment for the adult respiratory distress syndrome.

Author

Bernard GR

Address

Division of Pulmonary and Intensive Care Medicine, Vanderbilt University, Nashville, TN 37232.

Source

Eur Respir J Suppl, 1990 Oct, 11:, 496s-498s

Abstract

The adult respiratory distress syndrome (ARDS), often referred to as non-cardiac pulmonary oedema, is now regarded as a very complicated inflammatory process with oedema being only one facet. In recognition of this, pharmacologic therapy with anti-inflammatory corticosteroids was used widely until the completion of randomized clinical trials. Unfortunately, corticosteroids have not been proved to be useful in preventing ARDS in septic patients nor in patients with established ARDS and this has led to investigations with pharmacologic agents which are safer and more specifically targeted to certain parts of the inflammatory process. We have examined the role of the glutathione anti-oxidant system in the sheep model of ARDS as well as in patients with established ARDS through use of intravenous N-acetylcysteine (NAC). We have found that the response to endotoxin is markedly blunted in sheep treated with NAC. In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations, that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery, improved lung compliance and resolution of pulmonary oedema.

Language of Publication

English

Unique Identifier

91119633

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MeSH Heading (Major)

Acetylcysteine|*TU; Methylprednisolone|*TU; Respiratory Distress Syndrome, Adult|*DT

MeSH Heading

Animal; Comparative Study; Double-Blind Method; Free Radicals; Glutathione|BL; Human; Lymphocyte Transformation; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL

ISSN

0904-1850

Country of Publication

DENMARK

CAS Registry/EC Number

0 (Free Radicals); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione); 83-43-2 (Methylprednisolone)

Record 22 from database: MEDLINE
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Title

Bcl-2 functions in an antioxidant pathway to prevent apoptosis.

Author

Hockenbery DM; Oltvai ZN; Yin XM; Milliman CL; Korsmeyer SJ

Address

Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110.

Source

Cell, 1993 Oct 22, 75:2, 241-51

Abstract

Bcl-2 inhibits most types of apoptotic cell death, implying a common mechanism of lethality. Bcl-2 is localized to intracellular sites of oxygen free radical generation including mitochondria, endoplasmic reticula, and nuclear membranes. Antioxidants that scavenge peroxides, N-acetylcysteine and glutathione peroxidase, countered apoptotic death, while manganese superoxide dismutase did not. Bcl-2 protected cells from H2O2- and menadione-induced oxidative deaths. Bcl-2 did not prevent the cyanide-resistant oxidative burst generated by menadione. Two model systems of apoptosis showed no increment in cyanide-resistant respiration, and generation of endogenous peroxides continued at an inherent rate that was unaltered by Bcl-2. Following an apoptotic signal, cells sustained progressive lipid peroxidation. Overexpression of Bcl-2 functioned to suppress lipid peroxidation completely. We propose a model in which Bcl-2 regulates an antioxidant pathway at sites of free radical generation.

Language of Publication

English

Unique Identifier

94006556

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MeSH Heading (Major)

Apoptosis|*PH; Lipid Peroxidation|*PH; Oxygen|*ME; Proto-Oncogene Proteins|IP/*PH

MeSH Heading

Acetylcysteine|PD; Animal; Antioxidants; Base Sequence; Cell Compartmentation; Cell Line; Cell Survival; Cyanides|PD; Free Radicals; Glucocorticoids|DF; Glutathione Peroxidase|ME; Human; Interleukin-3|DF; Mice; Molecular Sequence Data; Oxygen Consumption; Recombinant Proteins|BI; Respiratory Burst|DE; Superoxide Dismutase|ME; Superoxides|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vitamin K|PD

Publication Type

JOURNAL ARTICLE

ISSN

0092-8674

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.11.1.9 (Glutathione Peroxidase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Antioxidants); 0 (Cyanides); 0 (Free Radicals); 0 (Glucocorticoids); 0 (Interleukin-3); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Proto-Oncogene Proteins); 0 (Recombinant Proteins); 11062-77-4 (Superoxides); 12001-79-5 (Vitamin K); 616-91-1 (Acetylcysteine); 7782-44-7 (Oxygen)

Record 23 from database: MEDLINE
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Title

HIV-Tat protein activates c-Jun N-terminal kinase and activator protein-1.

Author

Kumar A; Manna SK; Dhawan S; Aggarwal BB

Address

Department of Molecular Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Source

J Immunol, 1998 Jul, 161:2, 776-81

Abstract

Human immunodeficiency virus-1 tat (HIV-tat) protein, like other proinflammatory cytokines (such as TNF), activates a wide variety of cellular responses, some of which play a critical role in progression of HIV infection. Whether HIV-tat, like TNF, also activates c-Jun N-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 is not known. We show that treatment of human histiocytic lymphoma U937 cells with the HIV-tat protein causes activation of JNK and AP-1 in a time- and dose-dependent manner. Transfection of a T cell line, H9 cells with the HIV-tat gene also resulted in an activation of JNK that was not further increased by treatment of cells with exogenous HIV-tat protein. Neutralizing Ab against HIV-tat inhibited the HIV-tat-mediated JNK activation. The activation of JNK by HIV-tat appears to be mediated through generation of free radical species, since pretreatment of cells with N-acetylcysteine (NAC) abolished the effect. Overall our results demonstrate that HIV-tat activates JNK and AP-1, which may contribute to the pathogenesis of AIDS.

Language of Publication

English

Unique Identifier

98334029

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MeSH Heading (Major)

Ca(2+)-Calmodulin Dependent Protein Kinase|*ME; Gene Products, tat|GE/*PD/PH; HIV-1|GE/*IM; Transcription Factor AP-1|*ME

MeSH Heading

Cell Line; Enzyme Activation|DE/IM; Free Radicals|IM/ME; Genes, tat|IM; Human; Jurkat Cells; Kinetics; Protein Kinases|ME; Support, Non-U.S. Gov't; Transfection|IM

Publication Type

JOURNAL ARTICLE

ISSN

0022-1767

Country of Publication

UNITED STATES

Record 24 from database: MEDLINE
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Title

Hydrazine-mediated DNA damage: role of hemoprotein, electron transport, and organic free radicals.

Author

Runge Morris M; Wu N; Novak RF

Address

Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201.

Source

Toxicol Appl Pharmacol, 1994 Mar, 125:1, 123-32

Abstract

The hydrazines represent an important class of xenobiotic agents encountered in the environment, in industrial settings, and in medical therapeutics. Agents with a hydrazine functionality are metabolized to toxic intermediates capable of damaging cellular macromolecules and stimulating proteolysis. Phenylhydrazine (PH), methylhydrazine (MH), hydrazine (HY), and the therapeutic agents phenelzine (PZ) and hydralazine (HD) were examined for their ability to undergo metabolism via HbO2 and to cause damage to added supercoiled phi x174 RF DNA. The hydrazines, when incubated in hemolysate, caused a time- and concentration-dependent strand scission of DNA as monitored using phi x174 RF DNA. The rank order for hydrazine-mediated damage was phenylhydrazine > phenelzine > hydrazine > hydralazine > methylhydrazine. In addition, hydrazine-mediated damage to DNA increased in proportion to protein concentration (i.e., HbO2 content) of the hemolysate. To examine whether the DNA damage resulted primarily from organic free radicals or reactive oxygen free radical species, a series of mechanistic studies employing antioxidants and a free radical scavenger was initiated. The antioxidants dimethylfuran, dimethyl sulfoxide, and dimethylthiourea failed to inhibit hydrazine-mediated DNA damage in hemolysate. In contrast, the free radical spin trap agent dimethylpyrrolidin-N-oxide effectively inhibited PH-mediated DNA damage, while the free radical scavenger N-acetylcysteine also showed a protective effect against PH-, PZ-, HD-, HY-, and MH-mediated DNA strand scission. Potassium ferricyanide-mediated methemoglobin formation and imidazole, a ligand for the heme moiety of hemoglobin, both inhibited PH-stimulated DNA damage in hemolysate demonstrating the importance of oxyhemoglobin to the process. These results suggest that organic free radicals play a dominant role, relative to oxygen free radical species, in hydrazine-mediated DNA strand scission.

Language of Publication

English

Unique Identifier

94174570

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MeSH Heading (Major)

DNA Damage|*DE; DNA, Superhelical|*DE; Hemoglobins|*ME; Hydrazines|*TO

MeSH Heading

Electron Transport; Erythrocytes|ME; Free Radicals; Human; Hydralazine|TO; Monomethylhydrazine|TO; Phenelzine|TO; Phenylhydrazines|TO; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0041-008X

Country of Publication

UNITED STATES

Record 25 from database: MEDLINE
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Title

Nitric oxide modulates the c-Jun N-terminal kinase/stress-activated protein kinase activity through activating c-Jun N-terminal kinase kinase.

Author

Kim H; Shim J; Han PL; Choi EJ

Address

Cell Biology and Molecular Genetics Laboratories, Hanhyo Institute of Technology, Taejon, Korea.

Source

Biochemistry, 1997 Nov, 36:44, 13677-81

Abstract

Nitric oxide is a signaling molecule that has a broad range of physiological functions, including neurotransmission, macrophage activation, and vasodilation. The mechanism by which nitric oxide regulates signal transduction mediating diverse biological activities is not fully understood, however. Here, we demonstrate that nitric oxide induced the stimulation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in intact cells. Exposure of cultured HEK293 cells to sodium nitroprusside, a nitric oxide releasing agent, resulted in the stimulation of JNK1 activity. The sodium nitroprusside-induced stimulation of JNK1 activity was abolished by treatment of cells with N-acetylcysteine. Nitric oxide production from HEK293 cells ectopically expressing nitric oxide synthases resulted in the stimulation of JNK1 activity, while JNK1 stimulation in nitric oxide synthase-overexpressing cells was abrogated by a nitric oxide synthase inhibitor, NG-nitro-L-arginine. Furthermore, exposure of cells to sodium nitroprusside resulted in the stimulation of JNK kinase (JNKK1/SEK1). Taken together, our data suggest that nitric oxide modulates the JNK activity through activating JNKK1/SEK1.

Language of Publication

English

Unique Identifier

98022762

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MeSH Heading (Major)

Ca(2+)-Calmodulin Dependent Protein Kinase|*ME; Nitric Oxide|*ME; Protein Kinases|*ME

MeSH Heading

Animal; Cell Line; Enzyme Activation; Free Radicals|ME; Human; Kidney; Microglia; Nitroprusside; Rats; Stress|EN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transfection

Publication Type

JOURNAL ARTICLE

ISSN

0006-2960

Country of Publication

UNITED STATES

Record 26 from database: MEDLINE
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Title

Oxidized low-density lipoprotein induces the production of interleukin-8 by endothelial cells.

Author

Claise C; Edeas M; Chalas J; Cockx A; Abella A; Capel L; Lindenbaum A

Address

Department of Biochemistry, Hospital Antoine BÆeclÄere, Clamart, France.

Source

FEBS Lett, 1996 Dec, 398:2-3, 223-7

Abstract

The concentration of interleukin-8 (IL-8) and RANTES was measured in culture supernatants of human EA.hy 926 endothelial cells incubated with oxidized low-density lipoproteins (LDL). Oxidized LDL induced a 3-fold increase in IL-8 production (p < 0.01), whereas RANTES was not detected. Native LDL did not stimulate IL-8 production. IL-8 production in oxidized-LDL-treated cells was mediated by reactive oxygen species, as it was partially inhibited by catalase and completely inhibited by glutathione peroxidase and N-acetylcysteine (p < 0.01).

Language of Publication

English

Unique Identifier

97131600

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MeSH Heading (Major)

Endothelium, Vascular|CY/*ME; Interleukin-8|*BI; Lipoproteins, LDL|*PD

MeSH Heading

Antioxidants|PD; Catalase|ME; Cell Line; Dose-Response Relationship, Drug; Free Radicals|ME; Glutathione Peroxidase|ME; Human; Oxidation-Reduction; Reactive Oxygen Species|ME; RANTES|BI; Superoxide Dismutase|ME; Transforming Growth Factor beta|PD; Tumor Necrosis Factor|PD

Publication Type

JOURNAL ARTICLE

ISSN

0014-5793

Country of Publication

NETHERLANDS

Record 27 from database: MEDLINE
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Title

Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase.

Author

De Keulenaer GW; Chappell DC; Ishizaka N; Nerem RM; Alexander RW; Griendling KK

Address

Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Source

Circ Res, 1998 Jun, 82:10, 1094-101

Abstract

Atherosclerotic lesions are found opposite vascular flow dividers at sites of low shear stress and oscillatory flow. Since endothelial proinflammatory genes prominent in lesions are regulated by oxidation-sensitive transcriptional control mechanisms, we examined the redox state of cultured human umbilical vein endothelial cells after either oscillatory or steady laminar fluid shear stress. Endothelial oxidative stress was assessed by measuring activity of the superoxide (O2.- )-producing NADH oxidase (a major source of reactive oxygen species in vascular cells), intracellular O2.- levels, induction of the redox-sensitive gene heme oxygenase-1 (HO-1), and abundance of Cu/Zn superoxide dismutase (Cu/Zn SOD), an antioxidant defense enzyme whose level of expression adapts to changes in oxidative stress. When cells were exposed to oscillatory shear (+/-5 dyne/cm2, 1 Hz) for 1, 5, and 24 hours, NADH oxidase activity and the amount of HO-1 progressively increased up to 174+/-16% (P<0.05) and 505+/-111% (P<0.05) versus static conditions, respectively, whereas levels of Cu/Zn SOD remained unchanged. This upregulation of HO-1 was completely blocked by the antioxidant N-acetylcysteine (NAC, 20 mmol/L). In contrast, steady laminar shear (5 dyne/cm2) induced NADH oxidase activity and NAC-sensitive HO-1 mRNA expression only at 1 and 5 hours, a transient response that returned toward baseline at 24 hours. Levels of Cu/Zn SOD mRNA and protein were increased after 24 hours of steady laminar shear. Furthermore, intracellular O2.-, as measured by dihydroethidium fluorescence, was higher in cells exposed to oscillatory than to laminar shear. These data are consistent with the hypothesis that continuous oscillatory shear causes a sustained activation of pro-oxidant processes resulting in redox-sensitive gene expression in human endothelial cells. Steady laminar shear stress initially activates these processes but appears to induce compensatory antioxidant defenses. We speculate that differences in endothelial redox state, orchestrated by different regimens of shear stress, may contribute to the focal nature of atherosclerosis.

Language of Publication

English

Unique Identifier

98283481

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MeSH Heading (Major)

Endothelium, Vascular|*ME; Multienzyme Complexes|*ME; NADH, NADPH Oxidoreductases|*ME; Superoxides|*ME

MeSH Heading

Atherosclerosis|ME; Cells, Cultured; Free Radicals; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing)|GE/ME; Hemorheology; Human; Oxidation-Reduction; Stress, Mechanical; Superoxide Dismutase|GE/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0009-7330

Country of Publication

UNITED STATES

Record 28 from database: MEDLINE
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Title

Interferon-gamma inhibits insulin release and induces cell death in the pancreatic beta-cell line INS-1 independently of nitric oxide production.

Author

Laffranchi R; Spinas GA

Address

Department of Internal Medicine, University Hospital, ZÂurich, Switzerland.

Source

Exp Cell Res, 1997 Nov, 237:1, 217-22

Abstract

Interferon-gamma is among the cytokines which have been implicated as effector molecules of beta-cell destruction in autoimmune diabetes. Its mechanism of action is, however, largely unknown. In the present study rat pancreatic beta-cells, INS-1, were incubated with rat interferon-gamma (rIRN-gamma) for 24 h. rIFN-gamma at 1-1000 U/ml caused a dose-dependent inhibition of insulin release and cell metabolism with maximal inhibition being observed at 100 U/ml (insulin release: 51.2%, cell metabolism: 43.3% of control, respectively). In addition, 100 U/ml rIFN-gamma induced a 4- and 8.3-fold increase in apoptotic cell death after 24 and 48 h of incubation, respectively. These effects were not mediated by nitric oxide (NO), since IFN-gamma failed to induce nitric oxide synthase and NO production. Similarly, beta-cell dysfunction and death were not prevented by coincubation of the INS-1 cells with the poly(ADP-ribose) polymerase inhibitors benzamide, 3-aminobenzamide, and 4-aminobenzamide, the oxygen free radical scavenger Trolox, and the antioxidant N-acetylcysteine, indicating that NO, poly(ADP-ribose) polymerase, and oxygen free radicals are not involved in IFN-gamma induced beta-cell dysfunction and death.

Language of Publication

English

Unique Identifier

98085788

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MeSH Heading (Major)

Apoptosis|DE/*PH; Insulin|PD/*SE; Interferon-gamma, Recombinant|*PD; Islets of Langerhans|CY/*DE/PH; Nitric Oxide|*BI

MeSH Heading

omega-N-Methylarginine|PD; Acetylcysteine|PD; Animal; Antioxidants|PD; Benzamides|PD; Cells, Cultured; Chromans|PD; Free Radical Scavengers|PD; Human; Kinetics; NAD+ ADP-Ribosyltransferase|AI; Rats; Recombinant Proteins|PD; 4-Aminobenzoic Acid|AA/PD

Publication Type

JOURNAL ARTICLE

ISSN

0014-4827

Country of Publication

UNITED STATES

Record 29 from database: MEDLINE
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Title

Neutrophil function and glutathione-peroxidase (GSH-px) activity in healthy individuals after treatment with N-acetyl-L-cysteine.

Author

Urban T; Akerlund B; Jarstrand C; Lindeke B

Address

Apoteksbolaget AB, Huddinge Hospital, Sweden.

Source

Biomed Pharmacother, 1997, 51:9, 388-90

Abstract

The objective of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC) on neutrophilic functions and as an antioxidant. NAC, 600 mg daily, given orally to healthy individuals for a period of 2 weeks, affected some functions of human neutrophilic granulocytes when tested in vitro. NAC treatment caused a decrease in the production of superoxide anions by stimulated neutrophils and the improvement of their phagocytic capacity although it did not affect their random or chemotactic migration. The level of glutathione peroxidase (GSH-px) in thrombocytes of the NAC-treated individuals was increased in comparison with the activity before treatment. These results suggest that NAC might act as a scavenger of oxygen-derived free radicals released by stimulated neutrophils and thereby protect the tissue against the radical caused injury as well as optimize phagocytosis.

Language of Publication

English

Unique Identifier

98114878

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MeSH Heading (Major)

Acetylcysteine|AD/*PD; Free Radical Scavengers|AD/*PD; Glutathione Peroxidase|*ME; Neutrophils|*PH

MeSH Heading

Adult; Analysis of Variance; Healthy Worker Effect; Human; Middle Age; Phagocytosis|DE; Voluntary Workers

Publication Type

JOURNAL ARTICLE

ISSN

0753-3322

Country of Publication

FRANCE

Record 30 from database: MEDLINE
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Title

Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine.

Author

Nottet HS; van Asbeck BS; de Graaf L; de Vos NM; Visser MR; Verhoef J

Address

Eijkman-Winkler Laboratory for Medical Microbiology, University of Utrecht, The Netherlands.

Source

J Leukoc Biol, 1994 Dec, 56:6, 702-7

Abstract

N-acetyl-L-cysteine (NAC) has been proposed as a therapeutic agent for AIDS patients because it reduces human immunodeficiency virus type 1 (HIV-1) replication in stimulated T cells. However, NAC and glutathione enhanced acute HIV-1 replication in monocyte-derived macrophages. Buthionine sulfoximine did not affect NAC-mediated enhanced HIV-1 replication, indicating that the NAC-mediated effects are glutathione-independent. Superoxide dismutase and the hydroxyl radical scavengers dimethylthiourea and thiourea, but not urea, inhibited acute HIV-1 replication in macrophages. NAC reduced ferricytochrome c and increased dose-dependently Fe(III)-citrate and Fe(III)-EDTA-catalyzed hydroxyl radical formation in a system using glucose and glucose oxidase. Dimethylthiourea and thiourea, but not urea and superoxide dismutase, dose-dependently inhibited NAC-mediated enhancement of HIV-1 replication. These data suggest that oxygen radicals play an important role in self-sustained HIV-1 replication in macrophages and that oxygen radical scavengers other than NAC should be considered as therapeutic agents for AIDS patients.

Language of Publication

English

Unique Identifier

95088490

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MeSH Heading (Major)

Acetylcysteine|AI/*PD; HIV-1|*DE/ME/*PH; Macrophages|DE/ME/*VI; Reactive Oxygen Species|*ME; Virus Replication|*DE/*PH

MeSH Heading

Drug Interactions; Ferrous Compounds|ME; Free Radical Scavengers; Glutathione|PD; Human; Hydroxyl Radical|ME; Oxidation-Reduction; Stimulation, Chemical; Thiourea|AA/PD; Urea|PD

Publication Type

JOURNAL ARTICLE

ISSN

0741-5400

Country of Publication

UNITED STATES

Record 31 from database: MEDLINE
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Title

N-acetylcysteine (NAC) and glutathione (GSH): antioxidant and chemopreventive properties, with special reference to lung cancer.

Author

van Zandwijk N

Address

Department of Chest Oncology, HET Nederlands Kanker Institute, Amsterdam, The Netherlands.

Source

J Cell Biochem Suppl, 1995, 22:, 24-32

Abstract

Lung cancer arises as a focal transformation of chronically injured epithelium with cigarette smoke as one of its well-recognized causes. Apart from oxidants (free radicals), cigarette smoke contains such a multitude of (pre)carcinogens that it is astonishing that not every heavy smoker becomes a victim of malignancy. This points to the interindividual variability in susceptibility to carcinogens; several lines of evidence suggest that metabolic factors are involved in such variability. Metabolism of carcinogens as well as the subsequent (multi)steps of carcinogenesis are affected by host factors and governed by the balance between opposing forces, such as metabolic activation and detoxification, formation and scavenging of radicals, and DNA damage and repair, which seem to imply that carcinogenic compounds can initiate tumor growth only in amounts saturating detoxification mechanisms. In this context it is well known that glutathione (GSH) plays a crucial role in the detoxification of xenobiotics. N-Acetylcysteine (NAC), an aminothiol and synthetic precursor of intracellular cysteine and GSH, has been used for many years in Europe as a mucolytic drug. Clinically, it is a safe agent without major side effects and has been considered to have a place in cancer prevention, too. The antimutagenic and anticarcinogenic properties of NAC could be ascribed to multiple protective mechanisms, such as NAC nucleophilicity, antioxidant activity, its ability to act as a precursor of intracellular reduced GSH, modulation of detoxification, and DNA repair processes. On these grounds, NAC has emerged as a most promising cancer chemopreventive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

96010312

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MeSH Heading (Major)

Acetylcysteine|AE/*TU; Anticarcinogenic Agents|AE/*TU; Antioxidants|AE/*TU; Glutathione|AE/*TU; Lung Neoplasms|*PC; Smoking|*AE

MeSH Heading

Antidotes|TU; Expectorants|TU; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0733-1959

Country of Publication

UNITED STATES

Record 32 from database: MEDLINE
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Title

780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: involvement of reactive oxygen species.

Author

Grossman N; Schneid N; Reuveni H; Halevy S; Lubart R

Address

Skin Bank and Investigative Dermatology Laboratory, Soroka Medical Center and Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva, Israel. grossman@bgumail.bgu.ac.il

Source

Lasers Surg Med, 1998, 22:4, 212-8

Abstract

BACKGROUND AND OBJECTIVE: The purpose of this study was to determine irradiation parameters of a 780 nm low power CW diode laser (6.5 mW) leading to enhanced proliferation of cultured normal human keratinocytes (NHK). The possible role of reactive oxygen species (ROS) in this response was evaluated. STUDY DESIGN/MATERIALS AND METHODS: NHK were exposed to a single dose of 0 to 3.6 J/cm2 (0-180 sec) of irradiation. Proliferation parameters studied were: incorporation of 3H-thymidine during 6-24 hr following irradiation; percentage of dividing cells and number of cells, 24 hr and 48 hr following irradiation, respectively. RESULTS: Proliferation of NHK exposed to 0.45-0.95 J/cm2 was significantly enhanced by 1.3-1.9-folds relative to sham-irradiated controls, as inferred from parameters studied. Exposure to other energy densities was considerably less effective in enhancing proliferation parameters. Added enzymatic antioxidants, superoxide dismutase or catalase, scavenging superoxide anions and H2O2, suppressed this enhanced proliferation. Added scavengers (alpha-tocopherol acetate, scavenging lipid peroxidation, or sodium azide, histidine, mannitol, scavenging singlet oxygen, superoxide anions, and hydroxyl radicals, respectively), or N-acetyl cysteine, the thiol-reducing agent, suppressed the response, but to different extents. CONCLUSIONS: The results indicate that 780 nm low power diode laser irradiation enhanced keratinocytes proliferation in vitro, with an apparent involvement of ROS in this response, and comparably, might be used to promote their proliferation in vivo to enhance wound healing.

Language of Publication

English

Unique Identifier

98264421

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MeSH Heading (Major)

Keratinocytes|CY/DE/ME/*RE; Lasers|*; Reactive Oxygen Species|*PH

MeSH Heading

Acetates|PD; Acetylcysteine|PD; Antioxidants|PD; Catalase|PD; Cell Count; Cell Division|DE/RE; Cells, Cultured; Comparative Study; Enzyme Inhibitors|PD; Follow-Up Studies; Free Radical Scavengers|PD; Histidine|PD; Human; Hydrogen Peroxide|PD; Hydroxyl Radical|PD; Lipid Peroxidation; Mannitol|PD; Radiopharmaceuticals|DU; Sodium Azide|PD; Superoxide Dismutase|PD; Superoxides|PD; Support, Non-U.S. Gov't; Thymidine|ME; Tritium|DU; Vitamin E|PD

Publication Type

JOURNAL ARTICLE

ISSN

0196-8092

Country of Publication

UNITED STATES

Record 33 from database: MEDLINE
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Title

N-acetylcysteine in experimental and clinical acute lung injury.

Author

Bernard GR

Address

Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232.

Source

Am J Med, 1991 Sep 30, 91:3C, 54S-59S

Abstract

Clinically, lung injury is characterized by one or more of the following: altered gas exchange, dyspnea, decreased static compliance, and nonhydrostatic pulmonary edema. Although many antioxidants have been investigated in in vitro systems and in animal models, only some are at the developmental stage, or safe for clinical trials. Considerable evidence has recently accumulated supporting the hypothesis that leukocyte activation involves release of large quantities of highly reactive oxygen radicals, and hydrogen peroxide is partially responsible for diffuse microvascular and tissue injury in septic patients. Granulocyte depletion in animal models reduces the degree of fall in dynamic lung compliance and the increase in airflow resistance, lymph flow, and hypoxemia secondary to endotoxin administration. We hypothesized that the partial benefit derived from granulocyte depletion was due to the effective removal of a major source of oxygen radicals. Among the list of free radical scavengers, N-acetylcysteine stands out, because of its established usefulness in at least one human disease thought to be secondary to free radical organ damage (acetaminophen or paracetamol overdose). It is an extremely safe agent with a wide toxic-therapeutic window. An increasing number of animal studies indicate efficacy for this agent in the prevention and therapy of lung injury involving toxic oxygen species. We developed a randomized, double-blind protocol for the study of intravenous N-acetylcysteine in patients with established adult respiratory distress syndrome (ADRS). Results of this trial are preliminary. Nevertheless, they indicate that plasma and red cell glutathione levels are decreased in ADRS patients, and that N-acetylcysteine increases plasma cysteine as well as plasma and red cell glutathione. There are also indications that cardiopulmonary physiology is favorably affected by such therapy including improvements in chest radiograph edema scores, pulmonary vascular resistance, static compliance, oxygen delivery, and oxygen consumption.

Language of Publication

English

Unique Identifier

92026230

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MeSH Heading (Major)

Acetylcysteine|*TU; Free Radical Scavengers|*; Lung Diseases|*DT/ME; Respiratory Distress Syndrome, Adult|*DT

MeSH Heading

Animal; Clinical Trials; Endotoxins|PD; Glutathione|ME; Granulocytes|DE/ME; Human; Models, Biological; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9343

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Endotoxins); 0 (Free Radical Scavengers); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione)

Record 34 from database: MEDLINE
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Title

Free radical induced respiratory muscle dysfunction.

Author

Supinski G

Address

MetroHealth Medical Center, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Source

Mol Cell Biochem, 1998 Feb, 179:1-2, 99-110

Abstract

It is now recognized that respiratory muscle fatigue contributes to the development of respiratory failure in some patients with lung disease. This observation has prompted an examination into the mechanisms of development of muscle fatigue, with the understanding that an elucidation of these processes may lead to new therapeutic approaches to the treatment of these patients. A series of recent studies examining this issue have, moreover, discovered that oxygen-derived free radicals generated during strenuous contraction may modulate respiratory muscle contractile function and contribute to the development of muscle fatigue. The data supporting this concept include: (a) direct (e.g. EPR, ESR studies) and indirect (evidence of lipid peroxidation, protein carbonyl formation, glutathione oxidation) evidence that there is heightened free radical production in contracting muscle, (b) evidence that pharmacologic depletion of muscle antioxidant stores increases degree of muscle fatigue present after a period of exercise, and (c) evidence that administration of agents that act as free radical scavengers retard the development muscle fatigue. Free radicals may produce these changes in muscle force generating capacity by interacting with and altering the function of a number of intracellular-biophysical processes (i.e. sarcolemmal action potential propagation, sarcoplasmic reticulum calcium handling, mitochondrial function, contractile protein interactions).

Language of Publication

English

Unique Identifier

98202354

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MeSH Heading (Major)

Respiratory Muscles|*PA

MeSH Heading

Acetylcysteine|PD; Electron Spin Resonance Spectroscopy; Free Radicals|ME; Human; Hydroxyl Radical|ME; Muscle Contraction|PH; Muscle Fatigue|PH; Reactive Oxygen Species|ME; Superoxides|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-8177

Country of Publication

NETHERLANDS

Record 35 from database: MEDLINE
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Title

Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.

Author

Gillissen A; Nowak D

Address

Department of Internal Medicine, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany.

Source

Respir Med, 1998 Apr, 92:4, 609-23

Abstract

Reactive free oxygen radicals are known to play an important role in the pathogenesis of various lung diseases such as idiopathic pulmonary fibrosis (IPF), adult respiratory distress syndrome (ARDS) or cystic fibrosis (CF). They can originate from endogenous processes or can be part of exogenous exposures (e.g. ozone, cigarette smoke, asbestos fibres). Consequently, therapeutic enhancement of anti-oxidant defence mechanisms in these lung disorders seems a rational approach. In this regard, N-acetyl-L-cysteine (NAC) and ambroxol have both been frequently investigated. Because of its SH group, NAC scavenges H2O2 (hydrogen peroxide), .OH (hydroxol radical), and HOCl (hypochlorous acid). Furthermore, NAC can easily be deacetylated to cysteine, an important precursor of cellular glutathione synthesis, and thus stimulate the cellular glutathione system. This is most evident in pulmonary diseases characterized by low glutathione levels and high oxidant production by inflammatory cells (e.g. in IPF and ARDS). NAC is an effective drug in the treatment of paracetamol intoxication and may even be protective against side-effects of mutagenic agents. In addition NAC reduces cellular production of pro-inflammatory mediators (e.g. TNF-alpha, IL-1). Also, ambroxol [trans-4-(2-amino-3,5-dibromobenzylamino)-cyclohexane hydrochloride] scavenges oxidants (e.g. .OH, HOCl). Moreover, ambroxol reduces bronchial hyperreactivity, and it is known to stimulate cellular surfactant production. In addition, ambroxol has anti-inflammatory properties owing to its inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. For both substances effective anti-oxidant and anti-inflammatory function has been validated when used in micromolar concentrations. These levels are attainable in vivo in humans. This paper gives an up-to-date overview about the current knowledge of the hypothesis that oxidant-induced cellular damage underlies the pathogenesis of many human pulmonary diseases, and it discusses the feasibility of anti-oxidant augmentation therapy to the lung by using NAC or ambroxol.

Language of Publication

English

Unique Identifier

98323710

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MeSH Heading (Major)

Acetylcysteine|*TU; Ambroxol|*TU; Expectorants|*TU; Free Radical Scavengers|*TU; Lung Diseases|*DT/ME

MeSH Heading

Animal; Human; Lung|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0954-6111

Country of Publication

ENGLAND

Record 36 from database: MEDLINE
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Title

Oxidative stress leads to a rapid alteration of transferrin receptor intravesicular trafficking.

Author

Malorni W; Testa U; Rainaldi G; Tritarelli E; Peschle C

Address

Department of Ultrastructures, Istituto Superiore di Sanita, Rome, Italy. Malorni@mclink.it

Source

Exp Cell Res, 1998 May, 241:1, 102-16

Abstract

Several studies have demonstrated that perturbations of intracellular oxidative balance play a key role in numerous physiological as well as pathological conditions leading to various morbidity states. In previous studies we have shown that the free radical inducer menadione rapidly and specifically downmodulates the membrane transferrin receptor (TfR) by blocking receptor recycling. This modulation is due to receptor redistribution and not to receptor loss. Here we show that other oxidant compounds, such as hydrogen peroxide, also induce a rapid downmodulation of membrane TfR and that pretreatment of cells with the antioxidant, thiol supplier, N-acetylcysteine inhibits the downmodulation of these receptors elicited by either menadione or hydrogen peroxide. This observation suggests that intracellular thiol redox status may be a critical determinant of TfR downmodulation induced by oxidative stress. Furthermore, immunocytochemical results show that, in menadione-treated cells, TfRs are associated with the Golgi complex, where normally only 20% of total cellular TfRs is found and is mainly detected in the cytoplasm as scattered punctuations. Accordingly, menadione and hydrogen peroxide also elicited a downmodulation of low density lipoprotein receptor (LDLR) which mediates, like TfR, the transport of nutrients to the cell and is endocytosed through clathrin-coated pits. Finally, experiments carried out using okadaic acid, an inhibitor of phosphatases, suggest that H2O2 and menadione downmodulate surface TfR via different biochemical pathways. Taken together these results suggest the existence of a potentially important protective mechanism through which iron uptake is prevented in oxidatively imbalanced cells. Iron uptake can in fact give rise to the formation of highly toxic hydroxyl radicals reacting with hydrogen peroxide and leading to cytotoxicity. Downmodulation of surface TfR may thus represent the physiological control mechanism for reducing iron uptake in diverse pathological conditions including hypoxia-reperfusion injury, acquired immunodeficiency syndrome, and aging.

Language of Publication

English

Unique Identifier

98297174

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MeSH Heading (Major)

Intracellular Membranes|*CH/DE/ME; Oxidative Stress|*PH; Receptors, Transferrin|CH/DE/*ME

MeSH Heading

Acetylcysteine|PD; Cell Compartmentation; Down-Regulation (Physiology)|DE; Eukaryotic Cells|CH/DE; Exocytosis|DE; Free Radical Scavengers|PD; Hemostatics|PD; Human; Hydrogen Peroxide|PD; HL-60 Cells|CH/DE/ME; Oxidants|PD; Receptors, Cell Surface|DE/ME; Signal Transduction|DE; Support, Non-U.S. Gov't; Tumor Cells, Cultured|CH/DE/ME; Vitamin K|PD

Publication Type

JOURNAL ARTICLE

ISSN

0014-4827

Country of Publication

UNITED STATES

Record 37 from database: MEDLINE
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Title

Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication.

Author

Raju PA; Herzenberg LA; Herzenberg LA; Roederer M

Address

Department of Genetics, Beckman Center B007, Stanford University Medical School, California 94305-5125.

Source

AIDS Res Hum Retroviruses, 1994 Aug, 10:8, 961-7

Abstract

N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although both compounds blocked cytokine induction of HIV in acute and chronic infection models, and in HIV-LTR reporter cell systems, NAC was far more effective than OTC, even at suboptimal doses. To test whether this difference is due to GSH conversion efficacies of these compounds, we measured GSH restoration by NAC or OTC in GSH-depleted peripheral blood mononuclear cells (PBMCs), using flow cytometry. In isolated PBMCs, NAC fully replenishes depleted intracellular GSH whereas OTC only minimally replenishes GSH. This ability to replenish GSH in vitro and its ability to scavenge free radicals directly explain why NAC has more potent antiviral activities in vitro.

Language of Publication

English

Unique Identifier

95110643

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MeSH Heading (Major)

Acetylcysteine|*PD; Glutathione|*BI; HIV-1|*DE/PH; Thiazoles|*PD; Virus Replication|*DE

MeSH Heading

Antimetabolites|PD; Antioxidants|PD; Antiviral Agents|PD; Cells, Cultured; Comparative Study; Free Radical Scavengers|PD; Gene Expression Regulation, Viral|DE; Genes, Reporter; Human; HIV Long Terminal Repeat|GE; Leukocytes, Mononuclear|VI; Methionine Sulfoximine|AA/PD; Monocytes|VI; Prodrugs|PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor|PD

Publication Type

JOURNAL ARTICLE

ISSN

0889-2229

Country of Publication

UNITED STATES

Record 38 from database: MEDLINE
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Title

Modulation of potassium channels by protein tyrosine kinase inhibitors.

Author

Saad AH; Kuo SS; Koong AC; Hahn GM; Giaccia AJ

Address

Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468.

Source

J Cell Physiol, 1994 Oct, 161:1, 142-8

Abstract

Exposure of non-excitatory cells to the tyrosine kinase (PTK) inhibitors, genistein, herbimycin A, and tyrphostin, induced at least two families of K+ currents. The first, a TEA-insensitive slow-inactivating K+ current, is induced within 3 min following treatment with 140 mM genistein or 100 nM herbimycin A. The second current, a TEA-sensitive delayed rectifier, is induced within 30 min following treatment with 50 mM genistein or 10 nM herbimycin A. Currents with similar biophysical and pharmacological characteristics are induced in these cells following exposure to ionizing radiation. The radiation-induced currents are inhibited by pretreatment with the free radical scavenger, N-Acetyl L-Cysteine, or by pretreatment with the protein kinase C inhibitor, staurosporine; those induced by PTK inhibitors are not. The latter, therefore, do not appear to be mediated through free radicals or require serine/threonine phosphorylation for activation. Once the channels are activated by the PTK inhibitors, phosphorylation of the channel at serine/threonine residues results in slower inactivation of the induced current. We propose that protein tyrosine phosphorylation of the K+ channel protein itself or of a factor that interacts with it maintains the K+ channels of non-excitatory cells in a closed state. Following exposure to ionizing radiation, free radical-induced activation of serine/threonine kinase(s) results in phosphorylation of the channel and/or inactivation of a tyrosine kinase that in turn leads to activation of the K+ channels.

Language of Publication

English

Unique Identifier

95014751

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MeSH Heading (Major)

Potassium Channels|*DE/GE/PH; Protein-Tyrosine Kinase|*AI

MeSH Heading

Acetylcysteine|PD; Alkaloids|PD; Amino Acid Sequence; Calcium|PD; Cell Line; Electric Conductivity; Free Radical Scavengers|PD; Human; Immunoblotting; Molecular Sequence Data; Phosphoproteins|ME; Quinones|PD; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0021-9541

Country of Publication

UNITED STATES

Record 39 from database: MEDLINE
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Title

Studies on the role of oxygen radicals in asbestos-induced cytopathology of cultured human lung mesothelial cells.

Author

Gabrielson EW; Rosen GM; Grafstrom RC; Strauss KE; Harris CC

Address

Source

Carcinogenesis, 1986 Jul, 7:7, 1161-4

Abstract

The possible role of oxygen radicals in mediating the cytopathologic effects of asbestos was studied using human mesothelial cells in culture. Electron paramagnetic resonance measurements of intact cells using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide failed to detect any increase in oxygen radicals in mesothelial cells after exposure to amosite asbestos, although oxygen radicals were readily detected in cells exposed to menadione, an uncoupler of oxidation-reduction reactions. Cellular thiol levels were reduced after exposure to menadione, but were not affected by exposure to asbestos. Addition to the culture media of the free radical scavengers superoxide dismutase, reduced glutathione, N-acetylcysteine, or D-alpha-tocopherol had no affect on the dose-dependent cytotoxicity of amosite fibers. Furthermore, exposure of the mesothelial cells to amosite fibers resulted in no significant increase in the level of DNA single-strand breaks. These results all suggest that for cultured human mesothelial cells, oxygen free radicals are not important mediators of the cytopathic effect of asbestos.

Language of Publication

English

Unique Identifier

86245454

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MeSH Heading (Major)

Asbestos|*TO; Lung|CY/*DE; Oxygen|*

MeSH Heading

Cell Count; Cells, Cultured; DNA|AN; Electron Spin Resonance Spectroscopy; Free Radicals; Human; In Vitro; Spin Labels; Sulfhydryl Compounds|AN; Support, Non-U.S. Gov't; Vitamin K|TO

Publication Type

JOURNAL ARTICLE

ISSN

0143-3334

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 0 (Spin Labels); 0 (Sulfhydryl Compounds); 12001-79-5 (Vitamin K); 12172-73-5 (Asbestos, Amosite); 1332-21-4 (Asbestos); 7782-44-7 (Oxygen); 9007-49-2 (DNA)

Record 40 from database: MEDLINE
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Title

Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.

Author

Khechai F; Ollivier V; Bridey F; Amar M; Hakim J; de Prost D

Address

INSERM U294, CHU Xavier Bichat, Paris, France.

Source

Arterioscler Thromb Vasc Biol, 1997 Nov, 17:11, 2885-90

Abstract

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N-acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H2O2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.

Language of Publication

English

Unique Identifier

98073736

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MeSH Heading (Major)

Glycosylation End Products, Advanced|*PD; Monocytes|*DE/ME; Protein-Tyrosine Kinase|AI/*ME; Serum Albumin|*PD; Signal Transduction|*DE; Thromboplastin|*BI/GE

MeSH Heading

Acetylcysteine|PD; Antioxidants|PD; Diabetes Mellitus|CO; Enzyme Activation|DE; Enzyme Inhibitors|PD; Free Radical Scavengers|PD; Gene Expression Regulation|DE; Glycosylation; Human; Hydroxyl Radical|PD; Oxidative Stress; Phosphorylation; Protein Processing, Post-Translational; Quinones|PD; RNA, Messenger|BI; Support, Non-U.S. Gov't; Thrombophilia|ET/ME

Publication Type

JOURNAL ARTICLE

ISSN

1079-5642

Country of Publication

UNITED STATES

Record 41 from database: MEDLINE
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Title

Effect of oral N-acetylcysteine administration on human blood neutrophil and monocyte function.

Author

Jensen T; Kharazmi A; Schi‡tz PO; Nielsen H; Stenvang Pedersen S; Stafanger G; Koch C; H‡iby N

Address

Statens Seruminstitut, Department of Clinical Microbiology at Rigshospitalet, Copenhagen, Denmark.

Source

APMIS, 1988 Jan, 96:1, 62-7

Abstract

N-acetylcysteine (NAC) is known to be a scavenger of free oxygen radicals, and recent in vitro studies have demonstrated that it is also able to inhibit leukocyte function. The clinical significance of these effects is, however, not known. In this study we have measured the effect on human blood neutrophil and monocyte function of a single 400 mg dose of NAC administered orally. Administration of NAC to ten healthy volunteers resulted in significant reduction of neutrophil chemiluminescence response following activation by opsonized zymosan as compared to four non-treated persons acting as controls. No effect was observed on the chemotaxis of either cell type or on monocyte chemiluminescence response. These findings suggest that NAC may be beneficial in clinical conditions like cystic fibrosis, where tissue damage may be a consequence of the effects of increased release of toxic oxygen radicals and proteolytic enzymes.

Language of Publication

English

Unique Identifier

88149883

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MeSH Heading (Major)

Acetylcysteine|AD/*PD; Monocytes|*DE/PH; Neutrophils|*DE/PH

MeSH Heading

Administration, Oral; Chemotaxis, Leukocyte|DE; Human; Luminescence; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0903-4641

Country of Publication

DENMARK

CAS Registry/EC Number

616-91-1 (Acetylcysteine)

Record 42 from database: MEDLINE
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Title

Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury.

Author

Gonzalez PK; Zhuang J; Doctrow SR; Malfroy B; Benson PF; Menconi MJ; Fink MP

Address

Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215, USA.

Source

Shock, 1996, 6 Suppl 1:, S23-6

Abstract

Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further evaluation as therapeutic agents for treatment or prevention of sepsis-related ARDS in humans.

Language of Publication

English

Unique Identifier

96425752

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MeSH Heading (Major)

Lung|*IN/PA; Oxidative Stress|*; Respiratory Distress Syndrome, Adult|ET/PC/*PP

MeSH Heading

Acetylcysteine|TU; Adult; Animal; Catalase|TU; Disease Models, Animal; Endotoxins|TO; Ethylenediamines|TU; Free Radical Scavengers|TU; Human; Lipopolysaccharides|TO; Organometallic Compounds|TU; Reactive Oxygen Species|PH; Superoxide Dismutase|TU; Support, U.S. Gov't, P.H.S.; Swine; Thiourea|AA/TU

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1073-2322

Country of Publication

UNITED STATES

Record 43 from database: MEDLINE
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Title

Free-radical scavengers, thiol-containing reagents and endothelium-dependent relaxation in isolated rat and human resistance arteries.

Author

Sunman W; Hughes AD; Sever PS

Address

Department of Clinical Pharmacology, St Mary's Hospital, Imperial College of Science Technology and Medicine, London, U.K.

Source

Clin Sci (Colch), 1993 Mar, 84:3, 287-95

Abstract

1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force. 2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-omega-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone. 3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels. 4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-omega-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency. 5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation. 6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.

Language of Publication

English

Unique Identifier

93215202

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MeSH Heading (Major)

Acetylcysteine|*PD; Endothelium, Vascular|*PH; Isometric Contraction|*DE; Muscle, Smooth, Vascular|*DE/EN; Superoxide Dismutase|*PD

MeSH Heading

Acetylcholine|PD; Animal; Arginine|AA/PD; Arteries; Captopril|PD; Catalase|ME; Dose-Response Relationship, Drug; Drug Synergism; Female; Human; Male; Norepinephrine|PD; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't; Vascular Resistance|DE

Publication Type

JOURNAL ARTICLE

ISSN

0143-5221

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 50903-99-6 (NG-Nitroarginine Methyl Ester); 51-41-2 (Norepinephrine); 51-84-3 (Acetylcholine); 616-91-1 (Acetylcysteine); 62571-86-2 (Captopril); 7004-12-8 (Arginine)

Record 44 from database: MEDLINE
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Title

Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549.

Author

Koong AC; Giaccia AJ; Hahn GM; Saad AH

Address

Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468.

Source

J Cell Physiol, 1993 Aug, 156:2, 341-7

Abstract

Active oxygen species are generated in cells during pathophysiologic conditions such as inflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We investigated whether free radicals generated following exposure to hypoxia and reoxygenation activate voltage-dependent K+ ion channels in tumor cells in vitro. Using the technique of whole cell voltage clamping, we recorded currents from two families of potassium (K+) channels that were activated following reoxygenation. One of these groups possessed the electrophysical characteristics of a tetraethylammonium (TEA)-sensitive delayed rectifier channel and the other possessed characteristics of a Tea-insensitive slow inactivating channel. We present evidence which suggests that K+ channels are activated following reoxygenation but not during the hypoxia phase. The K+ currents decayed with time following reoxygenation. The decay characteristics of the K+ currents depended on the duration and level of hypoxia to which the cells were exposed. To determine whether activation of K+ channels by reoxygenation was initiated by free radicals, we pretreated cells with N-Acetyl L-Cysteine (NAC), a free radical scavenger, and found that this pretreatment abolished the currents induced by reoxygenation. We also present evidence that free radicals do not directly act on the channel itself, but activate a protein kinase which, in turn, activates the K+ channels. Taken together, these results indicate that one of the early responses to oxidative stress is the activation of K+ currents.

Language of Publication

English

Unique Identifier

93346485

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MeSH Heading (Major)

Adenocarcinoma|*PA/*PP/UL; Anoxia|*PP; Lung Neoplasms|*PA/*PP/UL; Potassium Channels|DE/*PH

MeSH Heading

Acetylcysteine|PD; Alkaloids|PD; Free Radical Scavengers; Human; Isoquinolines|PD; Oxidation-Reduction; Oxygen|ME; Piperazines|PD; Protein Kinases|AI/PH; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate|PD; Tetraethylammonium Compounds|PD; Time Factors; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0021-9541

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 2.7.1.37 (Protein Kinases); 0 (Alkaloids); 0 (Free Radical Scavengers); 0 (Isoquinolines); 0 (Piperazines); 0 (Tetraethylammonium Compounds); 16561-29-8 (Tetradecanoylphorbol Acetate); 616-91-1 (Acetylcysteine); 62996-74-1 (Staurosporine); 66-40-0 (tetraethylammonium); 7782-44-7 (Oxygen); 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-methylpiperazine)

Record 45 from database: MEDLINE
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Title

Induction of nuclear factor kappa B after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway.

Author

Mohan N; Meltz ML

Address

Department of Radiology, University of Texas Health Science Center, San Antonio 78284-7800.

Source

Radiat Res, 1994 Oct, 140:1, 97-104

Abstract

Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the kappa B transcription regulator in mitogen- or cytokine-stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca(++)-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-kappa B in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kappa B activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-dose ionizing radiation (0.1-2.0 Gy) activates kappa B transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-kappa B by low-dose ionizing radiation can be inhibited considerably by the antioxidant N-acetyl-L-cysteine, indicating that at least the major part of the activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the kappa B elements which in turn can serve as response elements for oxidant stress.

Language of Publication

English

Unique Identifier

95024639

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MeSH Heading (Major)

NF-kappa B|*ME/RE; Reactive Oxygen Species|*ME

MeSH Heading

Acetylcysteine|PD; Base Sequence; Cell Survival|RE; Cells, Cultured; DNA|ME; DNA Damage; Human; Hydrogen Peroxide|PD; Molecular Sequence Data; Support, U.S. Gov't, Non-P.H.S.; Tetradecanoylphorbol Acetate|PD

Publication Type

JOURNAL ARTICLE

ISSN

0033-7587

Country of Publication

UNITED STATES

Record 46 from database: MEDLINE
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Title

Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection.

Author

Dobmeyer TS; Findhammer S; Dobmeyer JM; Klein SA; Raffel B; Hoelzer D; Helm EB; Kabelitz D; Rossol R

Address

Department of Immunology, Paul-Ehrlich-Institute, Federal Agency for Sera and Vaccines, Langen, Germany.

Source

Free Radic Biol Med, 1997, 22:5, 775-85

Abstract

Programmed cell death (apoptosis) of T-lymphocytes observed in human immunodeficiency virus (HIV) infected individuals could be linked to oxidative stress. Therefore, we have investigated whether reactive oxygen species (ROS) induce apoptosis, which might contribute to the cell loss during progression of HIV-1 infection. ROS were generated in peripheral blood mononuclear cells (PBMC) obtained from HIV-1-positive patients and from healthy controls by stimulation with bacteria or by treatment with hypoxanthine/xanthine oxidase, which has been shown to generate ROS without direct involvement of cytokines. A dose-dependent inhibition of ROS formation correlated with the reduction of apoptosis induced by both bacterial and hypoxanthine/xanthine oxidase stimulation, suggesting that ROS generation was responsible for the induction of apoptosis. In addition, hydrogen peroxide (H2O2) rather than superoxide (O2.-) was observed to induce apoptosis. ROS-dependent apoptosis was shown to be independent of cytokines such as tumor necrosis factor-alpha (TNF-alpha). ROS-induced apoptosis was significantly enhanced in HIV-infected subjects even in the very early stages after infection. Moreover, ROS-mediated apoptosis was not restricted to a particular lymphocyte subset. In view of the diminished oxidative resistance of HIV-infected individuals, our results suggest that ROS-mediated apoptosis might contribute to the deletion of lymphocytes and to the pathogenesis of the disease.

Language of Publication

English

Unique Identifier

97165381

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MeSH Heading (Major)

Apoptosis|DE/*PH; HIV Infections|*ME/*PA; Lymphocytes|DE/*ME/*PA; Oxidative Stress|*

MeSH Heading

Acetylcysteine|PD; Adult; Antioxidants|PD; Catalase|PD; Free Radicals|ME; Glutathione|PD; Human; Hydrogen Peroxide|ME; HIV-1; In Vitro; Male; Reactive Oxygen Species|ME; Superoxide Dismutase|PD; Support, Non-U.S. Gov't; Tumor Necrosis Factor|PD

Publication Type

JOURNAL ARTICLE

ISSN

0891-5849

Country of Publication

UNITED STATES

Record 47 from database: MEDLINE
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Title

Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species.

Author

Lange RW; Hayden PJ; Chignell CF; Luster MI

Address

Environmental Immunology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. lange+@pitt.edu

Source

Inflamm Res, 1998 Apr, 47:4, 174-81

Abstract

OBJECTIVE AND DESIGN: Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs). MATERIALS AND METHODS: Anthralin was added to cultures of NHKs in the presence or absence of various antioxidants, including superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and relative changes in cytokine secretion and in the number of mRNA transcripts were examined. In addition, NHKs were either treated with neutralizing antibodies to tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter to establish the direct effects of anthralin on chemokine synthesis. RESULTS: Anthralin, at concentrations between 5 microM and 25 microM, caused a marked increase in granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, IL-8 and TNFalpha synthesis that was selectively inhibited by specific antioxidants. Furthermore, anthralin induced chemokine secretion without the need of primary cytokines. CONCLUSIONS: Taken together, these studies suggest that oxygen radicals generated from anthralin are responsible for the induction of inflammatory cytokines which, in turn contributes to their dermal toxicity.

Language of Publication

English

Unique Identifier

98290224

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MeSH Heading (Major)

Anthralin|*PD; Anti-Inflammatory Agents, Topical|*PD; Antioxidants|*PD; Cytokines|*BI; Keratinocytes|*DE/ME; Reactive Oxygen Species|*ME

MeSH Heading

Acetylcysteine|PD; Antibodies|PD; Cells, Cultured; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor|BI; Human; Interleukin-6|BI; Interleukin-8|BI; RNA, Messenger|ME; Superoxide Dismutase|PD; Thiourea|AA/PD; Transcription, Genetic|DE; Transfection; Tumor Necrosis Factor|BI; Vitamin E|PD

Publication Type

JOURNAL ARTICLE

ISSN

1023-3830

Country of Publication

SWITZERLAND

CAS Registry/EC Number

EC 1.15.1.1 (Superoxide Dismutase); 0 (Anti-Inflammatory Agents, Topical); 0 (Antibodies); 0 (Antioxidants); 0 (Cytokines); 0 (Interleukin-6); 0 (Interleukin-8); 0 (Reactive Oxygen Species); 0 (RNA, Messenger); 0 (Tumor Necrosis Factor); 1406-18-4 (Vitamin E); 2782-91-4 (tetramethylthiourea); 480-22-8 (Anthralin); 616-91-1 (Acetylcysteine); 62-56-6 (Thiourea); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)

Record 48 from database: MEDLINE
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Title

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

Author

Steib A; Freys G; Collin F; Launoy A; Mark G; Boudjema K

Address

Department of Anesthesiology, HÈopitaux Universitaires de Strasbourg, France.

Source

Liver Transpl Surg, 1998 Mar, 4:2, 152-7

Abstract

The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

Language of Publication

English

Unique Identifier

98192239

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MeSH Heading (Major)

Acetylcysteine|*TU; Hemodynamics|*DE; Liver|DE/*PH; Liver Transplantation|*

MeSH Heading

Adult; Aged; Female; Human; Liver Function Tests; Male; Middle Age; Prospective Studies; Time Factors

Publication Type

JOURNAL ARTICLE

ISSN

1074-3022

Country of Publication

UNITED STATES

Record 49 from database: MEDLINE
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Title

Oxygen free radicals and myocardial damage: protective role of thiol-containing agents.

Author

Ferrari R; Ceconi C; Curello S; Cargnoni A; Alfieri O; Pardini A; Marzollo P; Visioli O

Address

Cattedra di Cardiologia, Università degli Studi di Brescia, Italy.

Source

Am J Med, 1991 Sep 30, 91:3C, 95S-105S

Abstract

It has been suggested that the sudden presence of oxygen during reperfusion after a period of ischemia may be toxic for the myocardial cell. The oxygen molecule is capable of producing reactions in the cell, forming highly reactive free radicals, and inducing lipid peroxidation of membranes, altering their integrity and increasing their fluidity and permeability. The ischemic and reperfused cardiac cell is the prime candidate for this reaction sequence and may explain the molecular mechanism underlying the pathologic events related to membrane dysfunction and calcium homeostasis. However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites. The prerequisite for oxygen free radical involvement in ischemia and reperfusion damage is that ischemia alters the defense mechanisms against oxygen toxicity. It is known that ischemia may impair mitochondrial SOD and, with reperfusion, oxidative stress may occur as shown by tissue accumulation and release of oxidized glutathione. This tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme that removes hydrogen and lipid peroxides. Its formation and subsequent release is a reliable index of oxidative damage. In our study, we investigated the effects of N-acetylcysteine on oxidative damage in the isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and provides an important degree of protection against ischemia and reperfusion. Oxidative stress does not occur, mitochondrial function is maintained, enzyme release is reduced, and contractile recovery is increased. Similarly, we administered N-acetylcysteine in the pulmonary artery of coronary artery disease patients undergoing coronary bypass grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The degree of oxidative stress on reperfusion was reduced and recovery of cardiac function improved. In this article, we review the cardioprotective role of thiol-containing agents.

Language of Publication

English

Unique Identifier

92026237

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MeSH Heading (Major)

Antioxidants|ME/*TU; Myocardial Reperfusion Injury|*PC; Myocardium|*ME; Oxidants|*ME; Sulfhydryl Compounds|*TU

MeSH Heading

Animal; Coronary Disease|ME; Free Radicals|ME; Human; Models, Biological; Neutrophils|DE/ME; Oxygen|AI; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0002-9343

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Antioxidants); 0 (Free Radicals); 0 (Oxidants); 0 (Sulfhydryl Compounds); 7782-44-7 (Oxygen)

Record 50 from database: MEDLINE
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Title

Acetylcysteine: a drug with an interesting past and a fascinating future.

Author

Ziment I

Address

Source

Respiration, 1986, 50 Suppl 1:, 26-30

Abstract

N-acetylcysteine (NAC) possesses a free sulfhydryl group that can rupture disulfide bridges. Although it is considered to be a mucolytic, its mucokinetic actions include expectorant, bronchorrheic and mucoregulatory contributions. New uses include the management of acetaminophen poisoning and the scavenging of free radicals liberated by cancer chemotherapy drugs. The antioxidant effects may be of prophylactic value in lungs at risk from smoking, pollution and infection. Other uses proposed for NAC include the therapy of connective tissue diseases and its use as a component in life extension diets.

Language of Publication

English

Unique Identifier

87119434

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MeSH Heading (Major)

Acetylcysteine|AD/ME/*PD

MeSH Heading

Animal; Human; Mucus|DE

Publication Type

JOURNAL ARTICLE

ISSN

0025-7931

Country of Publication

SWITZERLAND

CAS Registry/EC Number

616-91-1 (Acetylcysteine)

Record 51 from database: MEDLINE
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Title

Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury.

Author

Chen X; Gresham A; Morrison A; Pentland AP

Address

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Source

Biochim Biophys Acta, 1996 Jan, 1299:1, 23-33

Abstract

UVB irradiation has previously been shown to significantly increase phospholipase activity and prostaglandin synthesis. Because UVB irradiation is a potent oxidative stress, the role of active oxygen species in regulating UV-induced cPLA2 synthesis and phosphorylation was examined. In the present study, irradiation produced a 3-fold increase in synthesis within 6 h following irradiation. Phosphorylation of cPLA2 was also increased to a similar extent. UVB-induced synthesis and phosphorylation of cPLA2 could be inhibited by pretreatment with the antioxidants 2,2,5,7,8-pentamethyl-6-hydroxychromane (50 microM) or N-acetylcysteine (10 mM). Treatment of unirradiated cultures with the potent oxidant tert-butyl hydroperoxide (500 microM) also increased cPLA2 synthesis and phosphorylation, suggesting that oxidative injury is an important regulator of cPLA2 synthesis. Increased synthesis of cPLA2 correlated well with increased [3H]arachidonic acid release, PGE2 synthesis and lipid peroxidation in epidermis after oxidant or UVB treatment. The results indicate that UVB-induced upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free radicals.

Language of Publication

English

Unique Identifier

96138524

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MeSH Heading (Major)

Oxidative Stress|*; Phospholipases A|*BI; Ultraviolet Rays|*

MeSH Heading

Acetylcysteine|PD; Antioxidants|PD; Arachidonic Acid|ME; Cells, Cultured|DE/RE; Cytosol|EN; Dinoprostone|BI; Enzyme Induction|DE/RE; Human; Lipid Peroxidation; Peroxides|PD; Phosphorylation; Skin|DE/RE; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0006-3002

Country of Publication

NETHERLANDS

Record 52 from database: MEDLINE
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Title

Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells.

Author

Bhunia AK; Han H; Snowden A; Chatterjee S

Address

The Johns Hopkins University School of Medicine, Lipid Research Atherosclerosis Unit, Department of Pediatrics, Baltimore, Maryland 21287-3654, USA.

Source

J Biol Chem, 1997 Jun, 272:25, 15642-9

Abstract

Previously, our laboratory reported that lactosylceramide (LacCer) stimulated human aortic smooth muscle cell proliferation via specific activation of p44 mitogen-activated protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and induced expression of the transcription factor c-fos downstream to the p44 MAPK signaling cascade (Bhunia A. K., Han, H., Snowden, A., and Chatterjee S. (1996) J. Biol. Chem. 271, 10660-10666). In the present study, we explored the role of free oxygen radicals in LacCer-mediated induction of cell proliferation. Superoxide levels were measured by the lucigenin chemiluminescence method, MAPK activity was measured by immunocomplex kinase assays, and Western blot analysis and c-fos expression were measured by Northern blot assay. We found that LacCer (10 microM) stimulates endogenous superoxide production (7-fold compared with control) in human aortic smooth muscle cells specifically by activating membrane-associated NADPH oxidase, but not NADH or xanthine oxidase. This process was inhibited by an inhibitor of NADPH oxidase, diphenylene iodonium (DPI), and by antioxidants, N-acetyl-L-cysteine (NAC) or pyrrolidine dithiocarbamate. NAC and DPI both abrogated individual steps in the signaling pathway leading to cell proliferation. For example, the p21(ras).GTP loading, p44 MAPK activity, and induction of transcription factor c-fos all were inhibited by NAC and DPI as well as an antioxidant pyrrolidine dithiocarbamate or reduced glutathione (GSH). In contrast, depletion of GSH by L-buthionine (S, R)-sulfoximine up-regulated the above described signaling cascade. In sum, LacCer, by virtue of activating NADPH oxidase, produces superoxide (a redox stress signaling molecule), which mediates cell proliferation via activation of the kinase cascade. Our findings may explain the potential role of LacCer in the pathogenesis of atherosclerosis involving the proliferation of aortic smooth muscle cells.

Language of Publication

English

Unique Identifier

97332642

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MeSH Heading (Major)

Lactosylceramides|*ME; Muscle, Smooth, Vascular|*ME; Signal Transduction|*

MeSH Heading

Acetylcysteine|ME; Antioxidants|PD; Buthionine Sulfoximine|ME; Ca(2+)-Calmodulin Dependent Protein Kinase|ME; Cell Division; Cells, Cultured; Enzyme Inhibitors|ME; Glutathione|ME; Guanosine Triphosphate|ME; Human; Multienzyme Complexes|ME; NADH, NADPH Oxidoreductases|ME; NADPH Oxidase|ME; Onium Compounds|ME; Oxidation-Reduction; Phosphorylation; Protein Kinase C|ME; Proto-Oncogene Proteins c-fos|ME; Superoxide Dismutase|ME; Superoxides|ME; Support, U.S. Gov't, P.H.S.; Xanthine Oxidase|ME

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

Record 53 from database: MEDLINE
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Title

Enhanced proteolysis and changes in membrane-associated calpain following phenylhydrazine insult to human red cells.

Author

Mortensen AM; Novak RF

Address

Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201.

Source

Toxicol Appl Pharmacol, 1991 Sep 15, 110:3, 435-49

Abstract

Phenylhydrazine-mediated protein damage in human red cells has been assessed using HPLC, one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblot analysis of major membrane proteins. The association of the Ca(2+)-activated neutral protease, calpain, with membrane proteins following hydrazine insult was also examined using immunoblot analysis. HPLC amino acid analysis of red cell suspensions was employed to quantify proteolysis. Phenylhydrazine (4 mM) increased the rate of leucine, lysine, and histidine release by approximately 12-, 7-, and 5-fold, respectively. N-acetylcysteine (20 mM), dithiothreitol (50 mM), and dimethylthiourea (50 mM) decreased the rate of phenylhydrazine-stimulated amino acid release by approximately 30-50%; in contrast, the free radical scavengers and antioxidants dimethylfuran (50 mM) and dimethyl sulfoxide (50 mM) were without significant effect. The calcium chelator, EGTA (10 mM) inhibited phenylhydrazine-stimulated proteolysis by approximately 30%. Phenylhydrazine (4 mM) caused attenuation of the major membrane protein bands present in the SDS-PAGE pattern and extensive smearing of a band in the region of approximately 28 kDa. Free radical scavengers and antioxidants failed to ameliorate significantly membrane protein damage in phenylhydrazine-treated cells as judged by SDS-PAGE. Immunoblot analysis of spectrin confirmed these results. Two-dimensional SDS-PAGE of membrane proteins following phenylhydrazine treatment, however, revealed the appearance of new protein spots and a loss of existing protein spots as compared to control. Western blot analysis of membrane-associated calpain (79 kDa (proenzyme), 77- and 75-kDa forms) was also performed. Phenylhydrazine-treated red blood cells exhibited concentration- and time-dependent changes in the level of membrane-associated procalpain relative to control. The inhibitors N-acetylcysteine, dithiothreitol, dimethylthiourea, and dimethyl sulfoxide in the presence of phenylhydrazine appeared to preserve the level of procalpain in association with the membrane proteins, but only N-acetylcysteine and dithiothreitol protected the 77- and 75-kDa forms. In contrast, dimethylfuran in the presence of phenylhydrazine caused a substantial decrease in all three forms of membrane-associated calpain. In phenylhydrazine-treated hemolysate, the level of the 77- and 75-kDa forms of membrane-associated calpain was decreased relative to control. These forms were absent when EGTA (10 mM) was included in the incubation and the level of proenzyme was decreased. These data suggest that calpain is recruited to the membrane following hydrazine insult, undergoes a Ca(2+)-dependent conversion to the active forms, and may be involved in the degradation of damaged cytosolic and membrane protein(s).

Language of Publication

English

Unique Identifier

92055715

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MeSH Heading (Major)

Blood Proteins|*DE/ME; Calpain|IM/IP/*ME; Erythrocyte Membrane|*DE/ME; Membrane Proteins|*DE/ME; Phenylhydrazines|*AE

MeSH Heading

Amino Acids|BL; Antibodies; Antioxidants|PD; Chromatography, High Pressure Liquid; Comparative Study; Egtazic Acid|PD; Electrophoresis, Polyacrylamide Gel; Erythrocytes|DE/ME; Free Radical Scavengers; Free Radicals|ME; Hemoglobins|DE; Human; Immunoblotting; Oxygen|ME; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0041-008X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.4.22.17 (Calpain); 0 (Amino Acids); 0 (Antibodies); 0 (Antioxidants); 0 (Blood Proteins); 0 (Free Radical Scavengers); 0 (Free Radicals); 0 (Hemoglobins); 0 (Membrane Proteins); 0 (Phenylhydrazines); 100-63-0 (phenylhydrazine); 67-42-5 (Egtazic Acid); 7782-44-7 (Oxygen)

Record 54 from database: MEDLINE
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Title

N-acetylcysteine inhibits apoptosis and decreases viral particles in HIV-chronically infected U937 cells.

Author

Malorni W; Rivabene R; Santini MT; Donelli G

Address

Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.

Source

FEBS Lett, 1993 Jul 19, 327:1, 75-8

Abstract

Apoptosis or programmed cell death (PCD) is a type of death occurring in various physiological processes. Several data suggest that: (1) apoptosis may play a critical role in AIDS pathogenesis; (2) an increase of endocellular free radical levels can be associated with activation of previously latent HIV virus. Tumor necrosis factor (TNF), a cytokine capable of inducing oxygen free radicals and apoptosis, appears also to be involved in HIV activation. The present findings, which elucidate a relationship between the percentage of apoptotic cells, reduced glutathione (GSH) depletion and an increase of p24 antigenemia, suggest that pretreatment with N-acetylcysteine (NAC) is capable of decreasing the above-mentioned phenomena in HIV-infected U937 cells.

Language of Publication

English

Unique Identifier

93327920

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MeSH Heading (Major)

Acetylcysteine|*PD; Apoptosis|*DE; HIV-1|*DE/GD

MeSH Heading

Cell Death|DE; Cell Line; DNA Damage|DE; Glutathione|ME; Hoe-33258; Human; HIV Core Protein p24|ME; Leukocytes, Mononuclear|MI; Microscopy, Fluorescence; Tumor Cells, Cultured; Tumor Necrosis Factor|PD

Publication Type

JOURNAL ARTICLE

ISSN

0014-5793

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (HIV Core Protein p24); 0 (Tumor Necrosis Factor); 23491-45-4 (Hoe-33258); 616-91-1 (Acetylcysteine); 70-18-8 (Glutathione)

Record 55 from database: MEDLINE
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Title

Nitrofurantoin-stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics.

Author

Novak RF; Kharasch ED; Wendel NK

Address

Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois.

Source

J Pharmacol Exp Ther, 1988 Nov, 247:2, 439-44

Abstract

Nitrofurantoin is an antimicrobial agent that causes nonimmune hemolytic anemia in susceptible populations and produces oxidant stress and cellular damage by mechanisms that differ from those associated with oxidants such as phenylhydrazine, which has been shown to stimulate proteolysis in red cells (Goldberg and Boches, 1982). Thus a study of the effects of nitrofurantoin on proteolysis in normal human red cells and red cell hemolysate has been conducted. Nitrofurantoin produced greater than a 3- and an approximately 5-fold increase in the rate of tyrosine release from red cells at 100 and 800 microM, respectively, compared with untreated red cells. In hemolysates nitrofurantoin also effectively increased proteolysis with a 2.4- and 4.0-fold increase in the rate of tyrosine release monitored at 100 and 800 microM, respectively, relative to controls. Stimulation of proteolysis by nitrofurantoin occurred linearly with time and with hematocrit over the range 5-25%. The rate of nitrofurantoin-stimulated proteolysis varied with glucose concentration in the incubation medium with a 2-fold increase in activity monitored between 2 and 10 mM glucose. Inhibitors of flavoprotein activity (electron transport), such as 2'-AMP and NADP, decreased nitrofurantoin-enhanced proteolysis in red cells to control levels, whereas methylene blue provided only a slight increase in proteolysis and an anaerobic environment (N2) stimulated significantly the rate of tyrosine production. Although N-acetylcysteine protected against the stimulation of proteolysis produced by 10 microM nitrofurantoin, this protective effect was diminished at higher concentrations of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

89036744

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MeSH Heading (Major)

Erythrocytes|*DE/EN; Nitrofurantoin|*TO; Peptide Hydrolases|*BL

MeSH Heading

Adenosine Triphosphate|BL; Adult; Ascorbic Acid|PD; Free Radicals; Glucose|PD; Glutathione|BL; Human; NADP|PD; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0022-3565

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.4 (Peptide Hydrolases); 0 (Free Radicals); 50-81-7 (Ascorbic Acid); 50-99-7 (Glucose); 53-59-8 (NADP); 56-65-5 (Adenosine Triphosphate); 67-20-9 (Nitrofurantoin); 70-18-8 (Glutathione)

Record 56 from database: MEDLINE
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Title

Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents.

Author

Doroshow JH

Address

Source

Biochem Biophys Res Commun, 1986 Feb 26, 135:1, 330-5

Abstract

This study investigated the effect of oxygen radical scavengers and iron chelating agents on the toxicity of doxorubicin for MCF-7 human breast cancer cells. Superoxide dismutase and catalase, but not the heat-inactivated enzymes, the hydroxyl radical scavenger N-acetylcysteine, and the organoselenium compound 2-phenyl-1-2-benzisoselenazol-3(2H)-o ne, which possesses glutathione peroxidase-like activity, significantly reduced or abolished tumor cell killing by doxorubicin. Similar protective activity was found only for those iron chelating agents capable of penetrating the tumor cell plasma membrane. These experiments suggest that an iron-dependent oxygen radical cascade contributes to the antineoplastic action of the anthracycline antibiotic doxorubicin.

Language of Publication

English

Unique Identifier

86158836

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MeSH Heading (Major)

Chelating Agents|*PD; Doxorubicin|AI/*TO; Oxygen|*TO

MeSH Heading

Breast Neoplasms; Catalase|ME; Cell Line; Cell Survival|DE; Cytoplasm; Extracellular Space; Female; Free Radicals; Human; Superoxide Dismutase|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0006-291X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Chelating Agents); 0 (Free Radicals); 23214-92-8 (Doxorubicin); 7782-44-7 (Oxygen)

Record 57 from database: MEDLINE
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Title

Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis: potential new use for an old drug.

Author

Henderson A; Hayes P

Address

Department of Intensive Care, Princess Alexandra Hospital, Brisbane, Australia.

Source

Ann Pharmacother, 1994 Sep, 28:9, 1086-8

Abstract

OBJECTIVE: To stimulate debate regarding a potential new use for acetylcysteine as a cellular antioxidant in severely septic patients with systemic inflammatory response syndrome (SIRS). DATA SOURCES: A MEDLINE review of published animal, human, and laboratory studies relating to the cytopathogenic effects of active radicals in SIRS and the protective effects of acetylcysteine and glutathione. STUDY SELECTION: Few studies were available so all studies pertinent to the objective were reviewed. DATA EXTRACTION: Clinical and basic science data from the available trials of the effects of acetylcysteine on active radical production or active radical cell injury were extrapolated to predict the effect of acetylcysteine on human sepsis. DATA SYNTHESIS: Severe sepsis is a major cause of SIRS. Much of the cellular injury associated with SIRS is mediated by active radicals produced by inflammatory cells that overwhelm endogenous antioxidants. Reduced glutathione is a crucial intracellular antioxidant that becomes depleted during SIRS. Regeneration of glutathione can be achieved by acetylcysteine, which unlike glutathione itself penetrates cells. In animal models of sepsis and lung injury, acetylcysteine mitigates the cytopathologic effects of SIRS. In humans, clinical benefit has been demonstrated in the SIRS of established fulminant hepatic failure. CONCLUSIONS: The data do not as yet lead to any firm conclusions regarding the value of acetylcysteine in the management of SIRS in severe sepsis. The animal and human studies are, however, sufficiently encouraging to warrant formal trials to test the hypothesis that acetylcysteine therapy has a cytoprotective effect in sepsis.

Language of Publication

English

Unique Identifier

95102183

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MeSH Heading (Major)

Acetylcysteine|PD/*TU; Antioxidants|PD/*TU; Sepsis Syndrome|DT/*PC

MeSH Heading

Animal; Comparative Study; Free Radicals; Glutathione|TU; Human

Publication Type

JOURNAL ARTICLE

ISSN

1060-0280

Country of Publication

UNITED STATES

Record 58 from database: MEDLINE
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Title

Inhibition of human platelet aggregation by endothelium-derived relaxing factor, sodium nitroprusside or iloprost is potentiated by captopril and reduced thiols.

Author

Mollace V; Salvemini D; Sessa WC; Vane JR

Address

William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.

Source

J Pharmacol Exp Ther, 1991 Sep, 258:3, 820-3

Abstract

We have examined whether inhibitors of angiotensin-converting enzyme-containing sulfhydryl groups such as, captopril (CPT) or SQ 14,534, the nonsulfhydryl-containing angiotensin-converting enzyme inhibitors, teprotide (TPR) or enalaprilat (ENA) and other structurally unrelated sulfhydryl-containing compounds, N-2-mercaptopropionylglycine (MPG) or N-acetyl-L-cysteine (NAC), could influence platelet aggregation. Incubation of human washed platelets with CPT, SQ 14,534, TPR, ENA, MPG or NAC (0.1-0.5 mM) did not modify their aggregatory responses to thrombin. However, the antiaggregatory properties of endothelial cells cultured from bovine aorta were potentiated by CPT, SQ 14,534, MPG or NAC but not by TPR or ENA (40-100 microM). CPT (100-500 microM) or NAC (50-200 microM) but not ENA (100 and 500 microM) also potentiated the antiaggregatory effects of sodium nitroprusside (1.0 microM) or iloprost (0.2 nM). The ability of the thiol-containing compounds (CPT or NAC) to potentiate the antiaggregatory effects of sodium nitroprusside or iloprost was not associated with an elevation of platelet cyclic GMP or cyclic AMP levels, respectively. Thus, CPT and other sulfhydryl-containing compounds can synergize with antiplatelet compounds, thereby enhancing the ability of endothelial-derived autocoids to inhibit platelet aggregation. The mechanism responsible for this potentiating effect of thiols on platelet aggregation is not known, but may relate to the ability of thiol-containing compounds to act as intracellular scavengers of oxygen-derived free radicals.

Language of Publication

English

Unique Identifier

91366609

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MeSH Heading (Major)

Captopril|*PD; Endothelium-Derived Relaxing Factor|*PD; Iloprost|*PD; Nitroprusside|*PD; Platelet Aggregation Inhibitors|*; Sulfhydryl Compounds|*PD

MeSH Heading

Acetylcysteine|PD; Blood Platelets|DE/ME; Drug Synergism; Enalaprilat|PD; Endothelium, Vascular|CY/PH; Human; Nucleotides, Cyclic|BL; Support, Non-U.S. Gov't; Teprotide|PD; Thrombin|PD

Publication Type

JOURNAL ARTICLE

ISSN

0022-3565

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.4.21.5 (Thrombin); 0 (Endothelium-Derived Relaxing Factor); 0 (Nucleotides, Cyclic); 0 (Platelet Aggregation Inhibitors); 0 (Sulfhydryl Compounds); 15078-28-1 (Nitroprusside); 35115-60-7 (Teprotide); 616-91-1 (Acetylcysteine); 62571-86-2 (Captopril); 78919-13-8 (Iloprost); 84680-54-6 (Enalaprilat)

Record 59 from database: MEDLINE
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Title

Drug antioxidant effects. A basis for drug selection?

Author

Halliwell B

Address

Pulmonary Medicine, UC Davis Medical Center, Sacramento.

Source

Drugs, 1991 Oct, 42:4, 569-605

Abstract

A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side-reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), alpha-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, alpha-tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug-derived radicals may occasionally cause significant damage.

Language of Publication

English

Unique Identifier

92137057

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MeSH Heading (Major)

Antioxidants|PD/*TU

MeSH Heading

Animal; Free Radicals; Human; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0012-6667

Country of Publication

NEW ZEALAND

CAS Registry/EC Number

0 (Antioxidants); 0 (Free Radicals)

Record 60 from database: MEDLINE
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Title

Sulfhydryl group in angiotensin converting enzyme inhibitors and superoxide radical formation.

Author

Mehta JL; Nicolini FA; Lawson DL

Address

Division of Cardiology, University of Florida College of Medicine, Gainesville.

Source

J Cardiovasc Pharmacol, 1990 Nov, 16:5, 847-9

Abstract

The superoxide radical scavenging effects of the SH group in the captopril molecule has been proposed to be the basis of the "cadioprotective" effect of this angiotensin converting enzyme (ACE) inhibitor in animal models of myocardial injury. We determined the effects of captopril, another ACE inhibitor with an SH group (SQ 26,703), its stereoisomer without ACE inhibitory effect but with an SH group (SQ 14,534), another ACE inhibitor without a SH group (enalaprilat), and N-acetylcysteine on superoxide radical generation by human neutrophils and by the purine-xanthine oxidase reaction. None of the compounds examined decreased superoxide radicals in therapeutic concentrations; however, SH-containing agents directly reduced spectrophotometric absorbance of ferricytochrome C. Thus, SH-containing agents with or without ACE inhibitory effects do not scavenge superoxide radicals.

Language of Publication

English

Unique Identifier

91116884

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MeSH Heading (Major)

Angiotensin-Converting Enzyme Inhibitors|*PD; Free Radical Scavengers|*; Superoxides|*ME

MeSH Heading

Captopril|PD; Free Radicals; Human; Sulfhydryl Compounds|PD

Publication Type

JOURNAL ARTICLE

ISSN

0160-2446

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Free Radical Scavengers); 0 (Free Radicals); 0 (Sulfhydryl Compounds); 11062-77-4 (Superoxides); 62571-86-2 (Captopril)

Record 61 from database: MEDLINE
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Title

Ebselen, a selenoorganic compound as glutathione peroxidase mimic.

Author

Sies H

Address

Institut für Physiologische Chemie I, Heinrich Heine Universität Düsseldorf, Germany.

Source

Free Radic Biol Med, 1993 Mar, 14:3, 313-23

Abstract

The selenoorganic compound ebselen, 2-phenyl-1,2-benzisoselenazol-3(2H)-one, exhibits activity as an enzyme mimic. The reaction catalyzed is that of a glutathione (GSH) peroxidase (i.e., the reduction of a hydroperoxide at the expense of thiol). The specificity for substrates ranges from hydrogen peroxide and smaller organic hydroperoxides to membrane-bound phospholipid and cholesterol hydroperoxides. In addition to glutathione, the thiol reductant cosubstrate can be dithioerythritol, N-acetylcysteine or dihydrolipoate, or other suitable thiol compounds. Ebselen also has properties such as free radical and singlet oxygen quenching. Model experiments in vitro with liposomes, microsomes, isolated cells, and organs show that the protection against oxidative challenge afforded by ebselen can be explained largely by the activity as GSH peroxidase mimic. Whether this also explains the known preliminary results in clinical settings is yet open. The metabolism and disposition of ebselen is presented in this review. The main point is that the selenium is not bioavailable, explaining the extremely low toxicity observed in animal studies. The occurrence of natural GPx mimics, ovothiol and related compounds, is briefly mentioned.

Language of Publication

English

Unique Identifier

93209580

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MeSH Heading (Major)

Azoles|CH/*ME/*PD; Glutathione Peroxidase|*ME; Organoselenium Compounds|CH/*ME/*PD

MeSH Heading

Animal; Antioxidants|CH/ME/PD; Free Radical Scavengers; Free Radicals|ME; Human; Lipid Peroxidation|DE; Oxidation-Reduction; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0891-5849

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.11.1.9 (Glutathione Peroxidase); 0 (Antioxidants); 0 (Azoles); 0 (Free Radical Scavengers); 0 (Free Radicals); 0 (Organoselenium Compounds); 60940-34-3 (ebselen)

Record 62 from database: MEDLINE
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Title

Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis.

Author

Weitzman SA; Stossel TP

Address

Source

J Immunol, 1982 Jun, 128:6, 2770-2

Abstract

Phagocytic leukocytes from normal humans can produce mutations in bacteria. To define further the role of oxygen radicals in this mutagenic process, we performed experiments in which scavengers or antioxidants were added to the incubation of phagocytes and bacteria. We found that 1) superoxide dismutase, catalase, mannitol, and benzoate were all capable of inhibiting mutation, 2) sulfhydryl compounds and vitamin E were also inhibitory, and 3) the presence of vitamin C in the incubations increased the mutation frequency. These data suggest an important role for hydroxyl radicals in mediating phagocyte-induced mutations.

Language of Publication

English

Unique Identifier

82191039

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MeSH Heading (Major)

Antioxidants|*PD; Oxygen|*ME; Phagocytes|*ME

MeSH Heading

Acetylcysteine|PD; Animal; Benzoates|PD; Catalase|PD; Cattle; Cysteine|PD; Free Radicals; Human; Mannitol|PD; Mutagenicity Tests; Salmonella|GE; Superoxide Dismutase|PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0022-1767

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); 0 (Antioxidants); 0 (Benzoates); 0 (Free Radicals); 4371-52-2 (Cysteine); 616-91-1 (Acetylcysteine); 65-85-0 (benzoic acid); 69-65-8 (Mannitol); 7782-44-7 (Oxygen)

Record 63 from database: MEDLINE
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Title

Oxidant stress and adult respiratory distress syndrome.

Author

Brigham KL

Address

Dept of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.

Source

Eur Respir J Suppl, 1990 Oct, 11:, 482s-484s

Abstract

Several experimental and theoretical lines of evidence implicate oxidant mechanisms in the diffuse lung injury which leads to the clinical syndrome called the adult respiratory distress syndrome (ARDS). The fact that the injury is characterized by diffuse lung inflammation and that neutrophils can injure lung cells by producing reactive oxygen species provide all of the events necessary for extracellular oxidant stress as an important mechanism of injury. In experimental models and in the clinical syndrome, biochemical evidence of oxidant injury can be measured in the form of lipid peroxidation products. In some models, antioxidants, even antioxidant enzymes which do not access cell interiors, can protect the lungs from injury. There is also evidence that reactive oxygen species generated within lung cells may provide an additional oxidant mechanism of injury. Gram negative bacterial endotoxin can directly injure lung endothelial cells in culture. This injury is unaffected by superoxide dismutase or catalase (antioxidant enzymes which do not enter cells), but is prevented by several antioxidants which penetrate cells (including dimethyl sulphoxide, dimethyl thiourea and allopurinol). The fact that allopurinol can inhibit direct lung cell injury by endotoxin suggests that xanthine oxidase may be a source of oxidant generation in lung endothelial cells. Current data suggest a two stage oxidant process of lung cell injury where there is both direct injury of the cell by intracellular generation of toxic oxidants and triggering of the inflammatory response. Activated inflammatory cells adherent to lung cells then enhance the injury by the generation and release of extracellular oxidants.

Language of Publication

English

Unique Identifier

91119630

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MeSH Heading (Major)

Lung|*PA; Oxygen|*AE; Respiratory Distress Syndrome, Adult|*/DT/ET

MeSH Heading

Acetylcysteine|TU; Animal; Free Radicals; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0904-1850

Country of Publication

DENMARK

CAS Registry/EC Number

0 (Free Radicals); 616-91-1 (Acetylcysteine); 7782-44-7 (Oxygen)

Record 64 from database: MEDLINE
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Title

Antioxidant-related parameters in patients treated for cancer chemoprevention with N-acetylcysteine.

Author

Bongers V; de Jong J; Steen I; de Vries N; Bast A; Snow GB; Braakhuis BJ

Address

Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands.

Source

Eur J Cancer, 1995 Jun, 31A:6, 921-3

Abstract

N-acetylcysteine (NAC) is an antioxidant, possibly effective in the early steps of carcinogenesis, and is applied to prevent second primary tumours in the upper aerodigestive tract and the lungs. In this study, we evaluated the pharmacodynamic profile of 600 mg NAC treatment, given daily for 3 months. Treatment caused a significant increase of the non-protein-SH concentration in blood plasma (38%) and erythrocytes (31%). Glutathione levels in exfoliated buccal mucosa cells appeared not to be influenced by treatment. The total radical-trapping ability parameter (TRAP) of blood plasma showed no change. In vitro, the addition of glutathione, but not of NAC did increase the TRAP value. In addition, when peroxyl radicals were generated in vitro, NAC was shown to be consumed more rapidly than glutathione. This suggests that NAC prevents early damage, while glutathione functions over a longer time period.

Language of Publication

English

Unique Identifier

95374827

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MeSH Heading (Major)

Cystine|*AA/PK/TU; Neoplasms|ME/*PC; Reactive Oxygen Species|*ME

MeSH Heading

Aged; Aged, 80 and over; Erythrocytes|ME; Female; Glutathione|ME; Human; Male; Middle Age; Mouth Mucosa|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0959-8049

Country of Publication

ENGLAND

Record 65 from database: MEDLINE
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Title

Nutritional antioxidants and the modulation of inflammation: theory and practice.

Author

Grimble RF

Address

Institute of Human Nutrition, University of Southampton, UK.

Source

New Horiz, 1994 May, 2:2, 175-85

Abstract

Highly potent substances are produced by the immune system. These substances include cytokines and oxidant molecules, such as hydrogen peroxide, free radicals, and hypochlorous acid. The purpose of immune cell products is to destroy invading organisms and damaged tissue, bringing about recovery. However, oxidants and cytokines can damage healthy tissue. Excessive or inappropriate production of these substances is associated with mortality and morbidity after infection and trauma, and in inflammatory diseases. Oxidants enhance interleukin-1, interleukin-8, and tumor necrosis factor production in response to inflammatory stimuli by activating the nuclear transcription factor, NF kappa B. Sophisticated antioxidant defenses directly and indirectly protect the host against the damaging influence of cytokines and oxidants. Indirect protection is afforded by antioxidants, which reduce activation of NF kappa B, thereby preventing up-regulation of cytokine production by oxidants. Cytokines increase both oxidant production and antioxidant defenses, thus minimizing damage to the host. While antioxidant defenses interact when a component is compromised, the nature and extent of the defenses are influenced by dietary intake of sulfur amino acids, for glutathione synthesis, and vitamins E and C. In animal studies, in vivo and in vitro responses to inflammatory stimuli are influenced by dietary intake of copper, zinc, selenium, N-acetylcysteine, cysteine, methionine, taurine, and vitamin E. Information from animal studies has yet to be fully translated into a clinical context. However, N-acetylcysteine, vitamin E, and a cocktail of antioxidant nutrients have reduced inflammatory symptoms in inflammatory joint disease, acute and chronic pancreatitis, and adult respiratory distress syndrome. Impaired antioxidant defenses may contribute to disease progression after infection with human immunodeficiency virus. Powerful arguments have been advanced for treatment with antioxidants to slow progression of acquired immunodeficiency syndrome.

Language of Publication

English

Unique Identifier

95006763

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MeSH Heading (Major)

Antioxidants|PD/*TU; Enteral Nutrition|*MT; Immunocompetence|*; Inflammation|*IM/ME/MO/*TH; Parenteral Nutrition, Total|*MT

MeSH Heading

Acquired Immunodeficiency Syndrome|IM/ME/MO/TH; Adaptation, Physiological; Animal; Cytokines|IM; Disease Models, Animal; Human; Infection|IM/ME/MO/TH; Multiple Trauma|IM/ME/MO/TH; Neoplasms|IM/ME/MO/TH; Oxidants

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1063-7389

Country of Publication

UNITED STATES

Record 66 from database: MEDLINE
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Title

Characterization of hydrazine-stimulated proteolysis in human erythrocytes.

Author

Runge-Morris MA; Iacob S; Novak RF

Address

Department of Pharmacology, Northwestern University, Chicago, Illinois 60611.

Source

Toxicol Appl Pharmacol, 1988 Jul, 94:3, 414-26

Abstract

The ability of hydrazine, acetylphenylhydrazine, methylhydrazine, and phenylhydrazine to stimulate proteolysis in red cells has been characterized. All four hydrazines effectively stimulated proteolysis in red cells and in hemolysate as evidenced by a two- to threefold increase in the rate of tyrosine release. The rate of tyrosine release varied linearly with time, increased with increasing concentration of hydrazine, and also increased as a function of hematocrit. The rank order for stimulation of proteolysis in red cells was phenylhydrazine greater than methylhydrazine greater than hydrazine approximately equal to acetylphenylhydrazine. Inhibitors of glycolysis in red cells only minimally (13-27%) decreased the rate of tyrosine release stimulated by the different hydrazines. Agents which diminished electron transport decreased the rate of tyrosine release. NADP inhibited the rate of tyrosine release stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 36 to 41%; 2'-AMP was less effective. The rate of tyrosine release resulting from insult by the hydrazines was increased slightly by methylene blue, moderately inhibited (approximately 10 to 27%) by the chelator o-phenanthroline and inhibited approximately 30 to 40% by N-ethylmaleimide. Use of an oxygen-depleted atmosphere (N2) increased slightly the rate of tyrosine release stimulated by the hydrazines; in contrast, carbon monoxide decreased proteolysis stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 50%. Although the antioxidants dimethylfuran, dimethylthiourea, and methylsulfoxide failed to diminish proteolysis stimulated by the hydrazines, N-acetylcysteine exerted a protective effect, decreasing hydrazine-stimulated tyrosine release in red cells approximately 30 to 50%. Inclusion of 3-amino-1,2,4-triazole in the incubation failed to increase further the rate of hydrazine-stimulated proteolysis. These data suggest that more reactive free radicals generated from the hydrazine are responsible for protein damage, that damaged protein (hemoglobin) is degraded via proteolysis, and that an ATP-independent process primarily participates in the degradation of abnormal proteins in the red cell. Thus, proteolytic enzymes present in the erythrocyte appear to exert a protective effect against cellular damage through the removal of abnormal proteins generated as a consequence of xenobiotic insult. The ability of proteolytic enzymes to recognize and degrade abnormal proteins may be of importance in using protein (hemoglobin)-xenobiotic adducts to assess exposure to toxic agents (risk assessment).

Language of Publication

English

Unique Identifier

88291087

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MeSH Heading (Major)

Blood Proteins|*ME; Erythrocytes|*DE/ME; Hydrazines|*TO

MeSH Heading

Adenosine Triphosphate|BI; Adult; Amitrole|PD; Antioxidants|PD; Calpain|ME; Electron Transport; Enzyme Precursors|ME; Human; Hydrogen Peroxide|PD; In Vitro; Methemoglobin|ME; Support, U.S. Gov't, P.H.S.; Tyrosine|ME

Publication Type

JOURNAL ARTICLE

ISSN

0041-008X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.4.22.- (procalpain); EC 3.4.22.17 (Calpain); 0 (Antioxidants); 0 (Blood Proteins); 0 (Enzyme Precursors); 0 (Hydrazines); 55520-40-6 (Tyrosine); 56-65-5 (Adenosine Triphosphate); 61-82-5 (Amitrole); 7722-84-1 (Hydrogen Peroxide); 9008-37-1 (Methemoglobin)

Record 67 from database: MEDLINE
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Title

A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress.

Author

Russo T; Zambrano N; Esposito F; Ammendola R; Cimino F; Fiscella M; Jackman J; OConnor PM; Anderson CW; Appella E

Address

Dipartimento di Biochimica e Biotecnologie Mediche, UniversitÄa degli Studi di Napoli, Federico II, Italy.

Source

J Biol Chem, 1995 Dec, 270:49, 29386-91

Abstract

Incubating human cells in diethylmaleate (DEM) depletes the intracellular pool of reduced glutathione (GSH) and increases the concentration of oxidative free radicals. We found that DEM-induced oxidative stress reduced the ability of p53 to bind its consensus recognition sequence and to activate transcription of a p53-specific reporter gene. Nevertheless, DEM treatment induced expression of WAF1/CIP1 but not GADD45 mRNA. The fact that N-acetylcysteine, a precursor of GSH that blocks oxidative stress, prevented WAF1/CIP1 induction by DEM suggests that WAF1/CIP1 induction probably was a consequence of the ability of DEM to reduce intracellular GSH levels. DEM induced WAF1/CIP1 expression in Saos-2 and T98G cells, both of which lack functional p53 protein. DEM treatment did not produce an increase in membrane-associated protein kinase C, but ERK2, a mitogen-activated protein kinase, was phosphorylated in a manner consistent with ERK2 activation. DEM treatment also produced a dose-dependent delay in cell cycle progression, which at low concentrations (0.25 mM) consisted of a G2/M arrest and at higher concentrations (1 mM) also involved G1 and S phase delays. Our results indicate that oxidative stress induces WAF1/CIP1 expression and arrests cell cycle progression through a mechanism that is independent of p53. This mechanism may provide for cell cycle checkpoint control under conditions that inactivate p53.

Language of Publication

English

Unique Identifier

96094335

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MeSH Heading (Major)

Cyclins|*BI/GE; Enzyme Inhibitors|*; Oxidative Stress|*; Protein p53|*PH

MeSH Heading

Animal; Base Sequence; Ca(2+)-Calmodulin Dependent Protein Kinase|ME; Cell Cycle|DE; Cells, Cultured; DNA|ME; Gene Expression Regulation|DE; Human; Maleates|PD; Molecular Sequence Data; Protein Kinase C|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

Record 68 from database: MEDLINE
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Title

Current theories and therapies relating to acute myocardial infarction and reperfusion injury.

Author

Stewart S

Address

Source

Intensive Crit Care Nurs, 1992 Jun, 8:2, 104-12

Abstract

Acute myocardial infarction (AMI) was previously treated with conservative strategies that allowed the process of ischaemia to proceed uninterrupted. The resultant myocardial necrosis and reduced ventricular function were accepted outcomes. The emergence of thrombolytic agents such as streptokinase and tissue plasminogen activator (tPA) revolutionised the management of coronary artery occlusion, yet the spectre of further myocardial necrosis and ventricular dysfunction remains. The concept of 'reperfusion injury', an acute process described as occurring after thrombolysis of a coronary artery occlusion and referring to an unexpected loss of ventricular function, has been extensively researched. Current research papers describing the mechanisms involved appear either to emphasise those processes that occur within the actual myocytes, or those events within the coronary vasculature. In most papers however, oxygen free radicals (OFRs) are accepted as mediators of cellular injury; despite the debate surrounding their primary source. Efforts to minimise the effects of primary ischaemia and subsequent 'reperfusion injury', appear to be focused upon restoring cardioprotection against the increased levels of these damaging molecules. Scavenging agents such as N-acetylcysteine (NAC) which can also assist in dilating coronary vessels as well as preventing further platelet aggregation, when combined with glyceryl trinitrate (GTN), are being closely scrutinised. Despite the advances made, the processes within the myocardium remain somewhat a mystery and the search continues for more effective strategies to ensure myocardial viability and long-term function. Critical care nurses need not only to be aware of the aim of these new strategies, but should also be conscious of their effect on the patients receiving them.

Language of Publication

English

Unique Identifier

92305605

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MeSH Heading (Major)

Myocardial Infarction|NU/PP/*TH; Myocardial Reperfusion|AE/*MT; Myocardial Reperfusion Injury|*ET/NU/PP

MeSH Heading

Electrocardiography; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0964-3397

Country of Publication

ENGLAND

Record 69 from database: MEDLINE
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Title

Paraquat poisoning. An overview of the current status.

Author

Bismuth C; Garnier R; Baud FJ; Muszynski J; Keyes C

Address

Clinique Toxicologique, Hôpital Fernand Widal, Paris, France.

Source

Drug Saf, 1990 Jul-Aug, 5:4, 243-51

Abstract

Paraquat is a bipyridyl compound with no known chronic toxicity or teratogenicity. It is poorly absorbed when inhaled, but causes severe illness when ingested orally, death usually occurring within 2 days of ingestion of 50 mg/kg. At lower doses death may be delayed for several weeks. The toxic compound accumulates in lung tissue where free radicals are formed, lipid peroxidation is induced and nicotinamide adenine dinucleotide phosphate (NADPH) is depleted. This produces diffuse alveolitis followed by extensive pulmonary fibrosis. The most important prognostic indicator is the quantity of paraquat absorbed, as shown by the plasma paraquat concentration. While renal failure will develop in the majority of those patients who eventually die, it may not, if present alone, indicate a fatal outcome. The absence of caustic burns in the upper digestive tract indicates a good prognosis. Treatment of paraquat poisoning remains ineffective, but Fuller's earth, activated charcoal and resins may prevent some absorption of the toxin. When tubular necrosis occurs, renal excretion of the compound decreases rapidly. A 3-compartment pharmacokinetic model has been described following ingestion of tracer doses including a 'deep' compartment for active pulmonary accumulation. Haemodialysis, haemoperfusion and forced dialysis have been attempted, with no clear improvement in survival rates. Superoxide dismutase, glutathione peroxidase, N-acetylcysteine and other 'free radical scavengers' have failed to alter the outcome in poisoned patients. Other theoretical treatments, such as deferoxamine, immunotherapy, NADPH repletion and lung transplantation still require clinical validation.

Language of Publication

English

Unique Identifier

90329177

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MeSH Heading (Major)

Paraquat|ME/PK/*PO

MeSH Heading

Charcoal|TU; Gastric Lavage; Hemodialysis; Human; Lipid Peroxidation; Lung|DE; Prognosis

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0114-5916

Country of Publication

NEW ZEALAND

CAS Registry/EC Number

16291-96-6 (Charcoal); 4685-14-7 (Paraquat)

Record 70 from database: MEDLINE
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Title

Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis.

Author

Louwerse ES; Weverling GJ; Bossuyt PM; Meyjes FE; de Jong JM

Address

Department of Neurology, Graduate School of Neurosciences Amsterdam, The Netherlands.

Source

Arch Neurol, 1995 Jun, 52:6, 559-64

Abstract

BACKGROUND: Free radicals may play a role in the pathogenesis of amyotrophic lateral sclerosis. OBJECTIVE: To investigate the efficacy of the free radical scavenging agent acetylcysteine in patients with amyotrophic lateral sclerosis. DESIGN: Randomized, double-blind, placebo-controlled clinical trial to assess the effect of treatment with acetylcysteine on survival and disease progression. SETTING: A university hospital referral setting. PATIENTS: One hundred ten consecutive patients who fulfilled the diagnostic criteria for amyotrophic lateral sclerosis, followed up at monthly intervals for 12 months. INTERVENTION: Acetylcysteine or placebo in a dose of 50 mg/kg per day subcutaneously for 12 months. MAIN OUTCOME MEASURE: Survival. RESULTS: After 12 months, 35 patients (65%) treated with acetylcysteine and 30 (54%) given placebo were still alive (hazard ratio, 0.74 in the acetylcysteine group relative to the placebo group; 95% confidence interval, 0.41 to 1.33; log-rank test, P = .31). Rates of disease progression, as expressed by decline in muscle strength, pulmonary function, disability, and bulbar function were similar in both groups. In the subgroup of 81 patients with limb onset of the disease, 28 patients (74%) in the acetylcysteine group and 22 (51%) in the placebo group survived 12 months (hazard ratio, 0.50; 95% confidence interval, 0.24 to 1.04; P = .06). In the bulbar subgroup of 29 patients, seven patients (44%) receiving acetylcysteine and eight (62%) receiving placebo were alive at the end of the study (hazard ratio, 1.66; 95% confidence interval, 0.56 to 4.99; P = .36). CONCLUSION: In this trial, treatment with the free radical scavenger acetylcysteine did not result in a major increase in 12-month survival or a reduction in disease progression in patients with amyotrophic lateral sclerosis.

Language of Publication

English

Unique Identifier

95283483

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MeSH Heading (Major)

Acetylcysteine|*TU; Amyotrophic Lateral Sclerosis|*DT/MO/PP

MeSH Heading

Double-Blind Method; Female; Human; Male; Middle Age; Placebos; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

0003-9942

Country of Publication

UNITED STATES

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