Toxic Metals

The Book
TOC Intro
Chapters:
1 2 3 4 5 6 7 8 9 10 11 12
13 14 15 16 17 18 19 20
21 22 23 24 25
A1 A2 A3 A4 A5 A6 Bib Karl

Vibrant Life Web

Family Of Three Chelation Formulas
Other VL Products
The Wednesday Letter
Frequently Asked Questions
Testimonials

Life Flow One, The Solution For Heart Disease Data Section

Shopping Cart

Use Separate Search Page or

Separate Search Page
or search below

Navigation Help

Ingredients
Technical

Write To Karl Loren

Table Of Contents

Toxic Metals Data

Life Flow One
The Solution For Heart Disease

by
Karl Loren

..1.. ..2.. ..3.. ..4.. ..5.. ..6.. ..7.. ..8.. ..9.. ..10.. ..11.. ..12.. ..13.. ..14.. ..15..

Top Of Menu

Click On The Number To View The Study Shown Under Description
Number	Description or Title	Comment
	Search Parameters Were: Results for your query: Search all fields for: n-acetylcysteine And free radicals Published in 1977 through 1999 Only select references with abstracts available Show references published in English only Show references pertaining to humans Documents: 1 to 70 of 70
...1...	Induction of p21 mediated by reactive oxygen species formed during the metabolism of aziridinylbenzoquinones by HCT116 cells.
...2...	Induction of p21 mediated by reactive oxygen species formed during the metabolism of aziridinylbenzoquinones by HCT116 cells.
...3...	Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril.
...4...	Effect of N-acetylcysteïne on Photofrin-induced skin photosensitivity in patients.
...5...	L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as precursors of intracellular glutathione in human peritoneal mesothelial cells.
...6...	Endogenous intracellular glutathionyl radicals are generated in neuroblastoma cells under hydrogen peroxide oxidative stress.
...7...	The effects of intravenous antioxidants in patients with septic shock.
...8...	Inhibitory effect of estrogens on the oxidative hemolysis induced by 2-amidinopropane hydrochloride, a free radical generator.
...9...	Effects of oxidants and antioxidants on nuclear factor kappa B activation in three different cell lines: evidence against a universal hypothesis involving oxygen radicals.
...10...	Effect of antioxidants on radical intensity and cytotoxic activity of eugenol.
Menu Position #10
...11...	Effect of cysteine, N-acetyl-L-cysteine and glutathione on cytotoxic activity of antioxidants.
...12...	Abnormalities of antioxidant metabolism in a case of Friedreich's disease.
...13...	Oxygen radical release by neutrophils of HIV-infected patients.
...14...	Role of oxygen radicals in 12-O-tetradecanoylphorbol-13-acetate-induced squamous differentiation of cultured normal human bronchial epithelial cells.
...15...	The role of oxygen-derived free radicals in the cytotoxicity of doxorubicin in multidrug resistant and sensitive human ovarian cancer cells.
...16...	Stimuli-induced superoxide radical generation in vitro by human alveolar macrophages from smokers: modulation by N-acetylcysteine treatment in vivo.
...17...	Lung protection by a thiol-containing antioxidant: N-acetylcysteine.
...18...	Effects of antioxidants on oxidant-induced sister chromatid exchange formation.
...19...	The role of oxidant injury in tumor cell sensitivity to recombinant human tumor necrosis factor in vivo. Implications for mechanisms of action.
...20...	Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages.
Menu Position #20
...21...	Potential of N-acetylcysteine as treatment for the adult respiratory distress syndrome.
...22...	Bcl-2 functions in an antioxidant pathway to prevent apoptosis.
...23...	HIV-Tat protein activates c-Jun N-terminal kinase and activator protein-1.
...24...	Hydrazine-mediated DNA damage: role of hemoprotein, electron transport, and organic free radicals.
...25...	Nitric oxide modulates the c-Jun N-terminal kinase/stress-activated protein kinase activity through activating c-Jun N-terminal kinase kinase.
...26...	Oxidized low-density lipoprotein induces the production of interleukin-8 by endothelial cells.
...27...	Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase.
...28...	Interferon-gamma inhibits insulin release and induces cell death in the pancreatic beta-cell line INS-1 independently of nitric oxide production.
...29...	Neutrophil function and glutathione-peroxidase (GSH-px) activity in healthy individuals after treatment with N-acetyl-L-cysteine.
...30...	Role for oxygen radicals in self-sustained HIV-1 replication in monocyte-derived macrophages: enhanced HIV-1 replication by N-acetyl-L-cysteine.
Menu Position #30
...31...	N-acetylcysteine (NAC) and glutathione (GSH): antioxidant and chemopreventive properties, with special reference to lung cancer.
...32...	780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: involvement of reactive oxygen species.
...33...	N-acetylcysteine in experimental and clinical acute lung injury.
...34...	Free radical induced respiratory muscle dysfunction.
...35...	Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy.
...36...	Oxidative stress leads to a rapid alteration of transferrin receptor intravesicular trafficking.
...37...	Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication.
...38...	Modulation of potassium channels by protein tyrosine kinase inhibitors.
...39...	Studies on the role of oxygen radicals in asbestos-induced cytopathology of cultured human lung mesothelial cells.
...40...	Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.
Menu Position #40
...41...	Effect of oral N-acetylcysteine administration on human blood neutrophil and monocyte function.
...42...	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.
...43...	Free-radical scavengers, thiol-containing reagents and endothelium-dependent relaxation in isolated rat and human resistance arteries.
...44...	Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549.
...45...	Induction of nuclear factor kappa B after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway.
...46...	Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection.
...47...	Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species.
...48...	Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?
...49...	Oxygen free radicals and myocardial damage: protective role of thiol-containing agents.
...50...	Acetylcysteine: a drug with an interesting past and a fascinating future.
Menu Position #50
...51...	Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury.
...52...	Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells.
...53....	Enhanced proteolysis and changes in membrane-associated calpain following phenylhydrazine insult to human red cells.
...54...	N-acetylcysteine inhibits apoptosis and decreases viral particles in HIV-chronically infected U937 cells.
...55...	Nitrofurantoin-stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics.
...56...	Prevention of doxorubicin-induced killing of MCF-7 human breast cancer cells by oxygen radical scavengers and iron chelating agents.
...57...	Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis: potential new use for an old drug.
...58...	Inhibition of human platelet aggregation by endothelium-derived relaxing factor, sodium nitroprusside or iloprost is potentiated by captopril and reduced thiols.
...59...	Drug antioxidant effects. A basis for drug selection?
...60...	Sulfhydryl group in angiotensin converting enzyme inhibitors and superoxide radical formation.
Menu Position #60
...61...	Ebselen, a selenoorganic compound as glutathione peroxidase mimic.
...62...	Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis.
...63...	Oxidant stress and adult respiratory distress syndrome.
...64....	Antioxidant-related parameters in patients treated for cancer chemoprevention with N-acetylcysteine.
...65...	Nutritional antioxidants and the modulation of inflammation: theory and practice.
...66...	Characterization of hydrazine-stimulated proteolysis in human erythrocytes.
...67...	A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress.
...68...	Current theories and therapies relating to acute myocardial infarction and reperfusion injury.
...69...	Paraquat poisoning. An overview of the current status.
...70...	Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis.
Menu Position #70

HealthGate Documents

Record 1 from database: MEDLINE
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top

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

Return To Top

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10

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

Return To Top
Return To Menu Position 10

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
Return To Top
Return To Menu Position 10
Return To Menu Position 20

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

Return To Top
Return To Menu Position 10
Return To Menu Position 20

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
Return To Top
Return To Menu Position 10
Return To Menu Position 20

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

Return To Top
Return To Menu Position 10
Return To Menu Position 20

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
Return To Top
Return To Menu Position 10
Return To Menu Position 20

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

Return To Top
Return To Menu Position 10
Return To Menu Position 20

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
Return To Top
Return To Menu Position 10
Return To Menu Position 20

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

Return To Top
Return To Menu Position 10
Return To Menu Position 20

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
Return To Top
Return To Menu Position 10
Return To Menu Position 20

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

Return To Top
Return To Menu Position 10
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

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
Return To Top
Return To Menu Position 20

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

Return To Top
Return To Menu Position 20

MeSH Heading (Major)