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Free Radicals &
Toxic Metals Data

Life Flow One
The Solution For Heart Disease

by
Karl Loren

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HealthGate Documents

Record 1 from database: MEDLINE
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Title

Nutrition and metal toxicity.

Author

Goyer RA

Address

National Institute of Environmental Health Sciences, Research Triangle Park, NC 27707.

Source

Am J Clin Nutr, 1995 Mar, 61:3 Suppl, 646S-650S

Abstract

Lead, cadmium, and mercury are toxic metals that are not essential for nutrition. However, the toxic effects of these metals may be mediated or enhanced by interactions or deficiencies of nutritionally essential metals. Lead competes with calcium, inhibiting the release of neurotransmitters, and interferes with the regulation of cell metabolism by binding to second-messenger calcium receptors, blocking calcium transport by calcium channels and calcium-sodium ATP pumps, and by competing for calcium-binding protein sites and uptake by mitochondria. Dietary deficiencies of calcium, iron, and zinc enhance the effects of lead on cognitive and behavioral development. Iron deficiency increases the gastrointestinal absorption of cadmium, and cadmium competes with zinc for binding sites on metallothionein, which is important in the storage and transport of zinc during development. Selenium protects from mercury and methyl mercury toxicity by preventing damage from free radicals or by forming inactive selenium mercury complexes.

Language of Publication

English

Unique Identifier

95185439

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MeSH Heading (Major)

Metals|*PO; Nutrition|*

MeSH Heading

Animal; Calcium|ME; Diet; Drug Interactions; Human; Iron|DF

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
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Title

Paramagnetic contrast agents in nuclear magnetic resonance medical imaging.

Author

Mendonça-Dias MH; Gaggelli E; Lauterbur PC

Address

Source

Semin Nucl Med, 1983 Oct, 13:4, 364-76

Abstract

Relaxation time differences are the sources of most of the contrast observed in proton NMR images, not only among normal organs and tissues but between lesions and the adjacent tissue. Although these differences are often large, there are low-contrast situations in which it would be desirable to increase the visibility of an organ or region. The study of time-dependent phenomena would also be aided by the ability to change selected relaxation times deliberately. One way to achieve these goals is to administer substances that change proton relaxation times in tissues without causing significant toxic effects or other physiologic changes. Paramagnetic ions and molecules, those with unpaired electrons, may be useful for this purpose because the very large magnetic effects associated with such electrons can drastically decrease water proton relaxation times at concentrations of the order of 100 to 1000 microM, which may be reached in certain organs after doses of 10 to 100 microM/kg. The general characteristics of such paramagnetic substances are described, and specific animal experiments with manganous ion and its complexes, and with stable nitroxide free radicals and molecular oxygen, are reviewed. The paramagnetic contrast agents already studied are effective, and many more are potentially possible, but the most important questions to be answered are whether acute and chronic toxicity are low enough to permit research and diagnosis on humans.

Language of Publication

English

Unique Identifier

84073202

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MeSH Heading (Major)

Contrast Media|*; Metals|*DU; Nuclear Magnetic Resonance|*DU

MeSH Heading

Animal; Dogs; Free Radicals; Human; Ions; Manganese|DU/TO; Metals, Rare Earth|DU/TO; Myocardial Infarction|DI; Oxygen; Support, U.S. Gov't, P.H.S.; Tromethamine|AA/DU

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0001-2998

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Contrast Media); 0 (Free Radicals); 0 (Ions); 0 (Metals); 0 (Metals, Rare Earth); 7365-44-8 (TES); 7439-96-5 (Manganese); 77-86-1 (Tromethamine); 7782-44-7 (Oxygen)

Record 3 from database: MEDLINE
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Title

Relationship between metal toxicity to subcellular systems and the carcinogenic response.

Author

Squibb KS; Fowler BA

Address

Source

Environ Health Perspect, 1981 Aug, 40:, 181-8

Abstract

The effects of metals on subcellular organelle functions have been reviewed in relation to carcinogenesis. Perturbations of the normal uptake and metabolism of carcinogens can arise through changes in microsomal enzyme activities, membrane permeabilities, and cell turnover. Metal effects on heme-dependent oxidative functions are well documented and are primarily manifested by increased heme degradation rates (microsomal heme oxygenase activity), decreased heme production (mitochondrial and cytosolic heme biosynthetic enzymes) and, in the case of a few metals, through nuclear effects of metals on the induction of microsomal enzymes. Many metals are accumulated by lysosomes, but known effects of metals on the function of these organelles in sequestering and storing organic compounds are few. Studies of changes in plasma or mitochondrial membrane permeabilities by metals have centered mainly on the susceptibility of membrane ATPase activities to metal ion alteration and on the involvement of metals in lipid peroxidation and free radical formation. Knowledge of the effects of metals on subcellular organelle functions should aid in the understanding of the mechanisms by which metal ions may play a role in the carcinogenic response.

Language of Publication

English

Unique Identifier

82004104

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MeSH Heading (Major)

Metals|*AE; Neoplasms|*CI/UL

MeSH Heading

Animal; Cell Membrane|DE; Cell Nucleus|DE; Endoplasmic Reticulum|DE; Human; Lysosomes|DE; Microsomes|DE; Mitochondria|DE; Proteins|BI

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0091-6765

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Metals)

Record 4 from database: MEDLINE
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Title

A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals.

Author

Chevion M

Address

Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.

Source

Free Radic Biol Med, 1988, 5:1, 27-37

Abstract

The metal-mediated site-specific mechanism for free radical-induced biological damage is reviewed. According to this mechanism, cooper- or iron-binding sites on macromolecules serve as centers for repeated production of hydroxyl radicals that are generated via the Fenton reaction. The aberrations induced by superoxide, ascorbate, isouramil, and paraquat are summarized. An illustrative example is the enhancement of double-strand breaks by ascorbate/copper. Prevention of the site-specific free radical damage can be accomplished by using selective chelators for iron and copper, by displacing these redox-active metals with other redox-inactive metals such as zinc, by introducing high concentrations of hydroxyl radicals scavengers and spin trapping agents, and by applying protective enzymes that remove superoxide or hydrogen peroxide. Histidine is a special agent that can intervene in free radical reactions in variety of modes. In biological systems, there are traces of copper and iron that are at high enough levels to catalyze free-radical reactions, and account for such deleterious processes. In the human body Fe/Cu = 80/1 (w/w). Nevertheless, both (free) copper and iron are soluble enough, and the rate constants of their reduced forms with hydrogen peroxide are sufficiently high to suggest that they might be important mediators of free radical toxicity.

Language of Publication

English

Unique Identifier

89326207

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MeSH Heading (Major)

DNA Damage|*; Free Radicals|*; Metals|*/ME

MeSH Heading

Animal; Human; Oxidation-Reduction; Oxygen|TO; 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; REVIEW; REVIEW, ACADEMIC

ISSN

0891-5849

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 0 (Metals); 7782-44-7 (Oxygen)

Record 5 from database: MEDLINE
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Title

Biochemical aspects of free radicals.

Author

Basaga HS

Address

Department of Science Education, Middle East Technical University, Ankara, Turkey.

Source

Biochem Cell Biol, 1990 Jul-Aug, 68:7-8, 989-98

Abstract

Toxic free radicals can be produced by many reactions required for the maintenance of normal metabolism and the production of energy in the cell. The reactivity of both primary and secondary radicals with biomolecules and in whole tissue systems is of interest, not only because of their importance in radiobiology but also because of the role these species play in toxicity and various disorders. Oxidant stress is known to increase the production of free radicals. In the presence of metals, especially iron, these radicals are converted into more damaging species. Trace elements play an important role in many systems that have evolved to deal with free radicals. The dietary status of the cell can affect the preventative antioxidant constituents of the cell. The chain-breaking antioxidant status can clearly be influenced by the dietary content of substances such as vitamins E and C.

Language of Publication

English

Unique Identifier

91025881

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MeSH Heading (Major)

Free Radicals|*

MeSH Heading

Animal; Antioxidants|ME; Disease|ET; Human; Metals|ME; Models, Chemical; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0829-8211

Country of Publication

CANADA

CAS Registry/EC Number

0 (Antioxidants); 0 (Free Radicals); 0 (Metals)

Record 6 from database: MEDLINE
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Title

The protective role of ceruloplasmin against the activity of free radicals in brain ischaemia.

Author

I…Áecka J

Address

Katedra i Klinika Neurologii Akademii Medycznej w Lublinie.

Source

Ann Univ Mariae Curie Sklodowska [Med], 1996, 51:, 97-101

Abstract

Free radicals are atoms, groups of atoms or particles having on their last orbital at least one unpaired electron. This feature decides about their great chemical reactivity and lability (12, 16). To potentially toxic oxygen radicals belong: peroxidal anion radical, hydroxidal radical, hydrogen peroxide, hydroxylic radical, peroxidal lipid radical, singletal oxygen (12). The presence of free radicals in biological systems may play a role in etiopathogenesis of different illnesses. Overactivity of these compounds causes damage of tissues and bodily organs (3, 16, 18).

Language of Publication

English

Unique Identifier

98128307

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MeSH Heading (Major)

Cerebral Ischemia|*PP; Ceruloplasmin|*PH

MeSH Heading

Biological Markers|AN; Cerebral Ischemia, Transient|PP; Free Radicals|ME; Human; Metals|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0066-2240

Country of Publication

POLAND

Record 7 from database: MEDLINE
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Title

Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent.

Author

Carter JD; Ghio AJ; Samet JM; Devlin RB

Address

National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

Source

Toxicol Appl Pharmacol, 1997 Oct, 146:2, 180-8

Abstract

Despite the many epidemiological studies supporting the contention that ambient air pollution particles can adversely affect human health, there is no clear agreement as to a biologically plausible mechanism which can explain the acute mortality and morbidity associated with exposure to particles less than 10 &mgr;m in size. We tested the hypothesis that metals present in an air pollution particle can induce the synthesis and expression of the inflammatory cytokines IL-8, IL-6, and TNFalpha. A residual oil fly ash (ROFA) containing the transition metals vanadium, nickel, and iron was used as a model emission source air pollution particle. Normal human bronchial epithelial (NHBE) cells were exposed for either 2 or 24 hr to 0, 5, 50, or 200 microg/ml ROFA. Concentrations of IL-8, IL-6, and TNF-alpha proteins were measured with commercially available ELISA kits. mRNA for these same cytokines was quantified by RT-PCR. NHBE cells exposed to ROFA produced significant amounts of IL-8, IL-6, and TNF, as well as mRNAs coding for these cytokines. Cytokine production was inhibited by the inclusion of either the metal chelator deferoxamine (1.0 mM) or the free radical scavenger dimethylthiourea (1.0 mM). In addition, vanadium containing compounds, but not iron or nickel sulfates, mimicked the effects of intact ROFA. These results demonstrate that metals present in ROFA may be responsible for production and release of inflammatory mediators by the respiratory tract epithelium and suggest that these mediators may contribute to the toxic effects of particulate air pollutants reported in epidemiology studies. Copyright 1997 Academic Press.

Language of Publication

English

Unique Identifier

98008957

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MeSH Heading (Major)

Air Pollutants, Occupational|*AE; Bronchi|*DE/ME; Cytokines|*BI/GE; Metals|*AE

MeSH Heading

Carbon|AE; Cells, Cultured; Chelating Agents|PD; Deferoxamine|PD; Epithelial Cells|DE/ME; Free Radical Scavengers|PD; Human; Interleukin-6|BI/GE; Interleukin-8|BI/GE; Iron|AE; Nickel|AE; Particle Size; RNA, Messenger|AN/GE; Thiourea|AA/PD; Tumor Necrosis Factor|BI/GE; Vanadium|AE

Publication Type

JOURNAL ARTICLE

ISSN

0041-008X

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
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Title

A mechanism for primaquine mediated oxidation of NADPH in red blood cells.

Author

Thornalley PJ; Stern A; Bannister JV

Address

Source

Biochem Pharmacol, 1983 Dec 1, 32:23, 3571-5

Abstract

The incubation of NADPH with primaquine results in the formation of free radicals which were demonstrated by the electron spin resonance (ESR) technique of spin trapping using 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) as the spin trap. The free radicals formed were identified as the superoxide (DMPO-OOH) and hydroxyl (DMPO-OH) spin adducts of DMPO. Copper/zinc superoxide dismutase inhibited the formation of DMPO-OOH while it only partly inhibited the formation of DMPO-OH which could be totally inhibited by catalase. This indicates that the formation of hydroxyl radicals is not totally arising from the Haber-Weiss reaction. However since the formation of hydroxyl radicals is dependent on hydrogen peroxide, a non-metal catalysed reduction of hydrogen peroxide is postulated for their formation. Oxygen consumption during the reaction between primaquine and NADPH was found to be consistent with the spin trapping experiments and the rate of production of DMPO-OH indicates the formation of 1:1 catalytic complex between the two reactants. Quenching of the fluorescence of NADPH at 460 nm in the presence of primaquine indicates the formation of a charge transfer complex. When red blood cells are incubated with primaquine a hydroxyl spin adduct (DMPO-OH) is observed. The formation of this radical is probably the main cause of primaquine mediated toxicity.

Language of Publication

English

Unique Identifier

84079996

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MeSH Heading (Major)

Erythrocytes|DE/*ME; NADP|*BL; Primaquine|BL/*PD

MeSH Heading

Cyclic N-Oxides|CYCLIC OXIDES N; Electron Spin Resonance Spectroscopy; Free Radicals; Human; In Vitro; Oxidation-Reduction; Oxygen Consumption|DE; Spectrometry, Fluorescence; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0006-2952

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Cyclic N-Oxides); 0 (Free Radicals); 3317-61-1 (5,5-dimethyl-1-pyrroline-1-oxide); 53-59-8 (NADP); 90-34-6 (Primaquine)

Record 9 from database: MEDLINE
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Title

Hemin toxicity in a human epithelioid sarcoma cell line.

Author

Braverman S; Helson C; Helson L

Address

St. Agnes Hospital, White Plains, New York 10605, USA.

Source

Anticancer Res, 1995 Sep, 15:5B, 1963-7

Abstract

The major cytotoxic component of hemin was identified as metal free protoporphyrin IX in an epithelioid sarcoma cell line (VA-ES-BJ) and a glioblastoma cell line (U-373 MG) by exposing the cell lines to the iron chelator deferoxamine, tin-protoporphyrin IX, and protoporphyrin IX. The contribution of lipid peroxidation and free radical generation to toxicity was examined using DL-buthionine-[S,R]-sulfoximine (BSO), and 21-aminosteroid (lazaroid, U74500A). Hemin caused significantly greater toxicity in VA-ES-BJ than in U-373 MG. While exogenous PpIX was more toxic than hemin in both cell lines, this toxicity was not due to iron depletion following intracellular heme formation since ferric citrate did not reverse PpIX toxicity. Pre-treatment with BSO enhanced hemin toxicity in the VA-ES-BJ cell line but not in U-373 MG, suggesting different modes of toxicity in the two cell lines. Exposure to lazaroid protected only VA-ES-BJ from protoporphyrin-induced toxicity implicating a specific sensitivity to lipid peroxidation and/or free radical generation by this cell line. These characteristics of the VA-ES-BJ cell line distinguish it from the glioblastoma and emphasize its utility for exploring cytotoxic effects of hemin and its precursors.

Language of Publication

English

Unique Identifier

96152426

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MeSH Heading (Major)

Hemin|*PD

MeSH Heading

Cell Survival|DE; Deferoxamine|PD; Human; Iron|ME; Lipid Peroxidation; Methionine Sulfoximine|AA/PD; Protoporphyrins|PD; Sarcoma|PA; Support, Non-U.S. Gov't; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0250-7005

Country of Publication

GREECE

Record 10 from database: MEDLINE
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Title

The antioxidant vitamins.

Author

Johnson FC

Address

Source

CRC Crit Rev Food Sci Nutr, 1979, 11:3, 217-309

Abstract

This article is an attempt to study the metabolic functions of vitamin C and E together. Such a study must necessarily be incomplete owing to the extreme richness of the literature. The increasing importance of the work on free radical reactions, their toxicity and carcinogenic action, and also their relation to the metabolism of metals, particularly iron, copper, selenium, and zinc, shows a number of metabolic pathways with which both vitamins interact. It is hoped that this article will indicate future research possibilities.

Language of Publication

English

Unique Identifier

79212399

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Menu Position #10

MeSH Heading (Major)

Antioxidants|*/ME; Ascorbic Acid|*ME/TU; Vitamin E|*ME/TU

MeSH Heading

Adolescence; Adult; Animal; Ascorbic Acid Deficiency|ME; Chemistry; Dehydroascorbic Acid; Fatty Acids, Unsaturated|ME; Female; Fertility|DE; Food Analysis; Food Handling; Free Radicals; Heat; Human; Leukocytes|ME; Male; Metabolic Detoxication, Drug; Nutritional Requirements; Pregnancy; Sex Factors; Species Specificity; Structure-Activity Relationship; Trace Elements|ME; Vitamin E Deficiency|ME

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0099-0248

Country of Publication

UNITED STATES

Record 11 from database: MEDLINE
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Title

Activation of human monocytes with lipopolysaccharide induces metallothionein expression and is diminished by zinc.

Author

Leibbrandt ME; Koropatnick J

Address

Department of Pathology, University of Western Ontario, London, Canada.

Source

Toxicol Appl Pharmacol, 1994 Jan, 124:1, 72-81

Abstract

The metal-binding protein metallothionein (MT) confers resistance to the toxic effects of metals. Although a role for MT in metal homeostasis and protection against toxic free radicals has been suggested, no clear physiological function has been established. The ability of human monocytes to be activated by bacterial lipopolysaccharide (LPS) treatment provided a model to investigate the effect of zinc on both cellular activation (H2O2 production) and MT expression. In both primary human monocytes and a monocyte-derived cell line (THP-1), LPS induced activation and MT expression; it did not induce MT expression in nonmonocyte human cells. Treatment of THP-1 cells with nontoxic zinc levels increased MT accumulation. Subsequent treatment with LPS resulted in a decrease in both MT mRNA and protein levels and inhibited the ability of THP-1 cells to undergo the respiratory burst. Pretreatment with cadmium had the same inhibitory effect. We conclude that MT expression is associated with monocyte activation, and exposure to zinc or cadmium interferes with the ability of monocytes to respond to activation signals. Metallothionein may play a role in that response.

Language of Publication

English

Unique Identifier

94120527

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Menu Position #10

MeSH Heading (Major)

Lipopolysaccharides|*PD; Lymphocyte Transformation|*DE/*PH; Metallothionein|*BI/DE/GE; Zinc|*PD

MeSH Heading

Base Sequence; Cadmium|PD; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor|PD; Human; Hydrogen Peroxide|AN; Molecular Sequence Data; Monocytes|DE/PH; Polymerase Chain Reaction; RNA, Messenger|AN; Support, Non-U.S. Gov't; Tetradecanoylphorbol Acetate|PD; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0041-008X

Country of Publication

UNITED STATES

Record 12 from database: MEDLINE
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Title

Oxygen toxicity: an introduction.

Author

Bostek CC

Address

Source

AANA J, 1989 Jun, 57:3, 231-7

Abstract

Although oxygen has been known to be toxic for more than 200 years, the clinical importance of oxygen toxicity was not appreciated until an epidemic of retrolental fibroplasia occurred in the early 1950s. Oxygen at high partial pressures is toxic to the respiratory, cardiovascular, nervous, and gastrointestinal systems. Toxicity results from the formation of oxygen-free radicals. These arise within mitochondria as oxygen is reduced to water, as byproducts of prostaglandin and thromboxane synthesis, and by the xanthine oxidase catalyzed reduction of xanthine or hypoxanthine. They are also produced by activated macrophages as part of the immune response. Superoxide anion is the radical most commonly produced. It dismutes to hydrogen peroxide, which is able to diffuse through lipid membranes. Hydrogen peroxide reacts with transition metals to produce the highly reactive hydroxyl radical which can initiate chain reactions of lipid peroxidation leading to cell rupture. Oxygen radical scavengers such as superoxide dismutase and catalase protect the body against normal levels of oxygen-free radicals. Oxygen toxicity can result from either reperfusion of ischemic tissue or prolonged exposure to high concentrations of oxygen. Limiting hyperoxia to maintain arterial oxygen percent saturation (SaO2) greater than or equal to 90% is recommended.

Language of Publication

English

Unique Identifier

89370953

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Menu Position #10

MeSH Heading (Major)

Free Radicals|*; Oxygen|ME/*PO

MeSH Heading

Animal; Dogs; Human; Lung Diseases|CI; Oxygen Inhalation Therapy|NU; Rats; Reperfusion Injury|CI

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0094-6354

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 7782-44-7 (Oxygen)

Record 13 from database: MEDLINE
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Title

Free radicals and environmental toxins.

Author

Thomas CE; Aust SD

Address

Source

Ann Emerg Med, 1986 Sep, 15:9, 1075-83

Abstract

Some chemicals that contaminate our environment exert their toxic effects by virtue of their ability to form free radicals. In the absence of sufficient quenching reactions, these reactive radicals can attack biomolecules, resulting in their oxidative degradation. Biological membranes which contain polyunsaturated fatty acids are most susceptible to oxidative degradation (lipid peroxidation), although oxidation of DNA may have more severe biological consequences. Free radicals species can be generated by at least two mechanisms in vivo. The first, of which carbon tetrachloride (CCl4) is the classic example, is the biotransformation of the chemical to a free radical species. Metabolism of CCl4 to the trichloromethyl radical by the hepatic mixed-function oxidase system results in the initiation of lipid peroxidation, protein-lipid cross linkages, and trichloromethyl adducts with DNA, protein, and lipid. The second mechanism for forming free radicals involves their reduction to less stable free radical intermediates which are oxidized by molecular oxygen to give superoxide (O2-.). In the presence of transition metals, such as iron, O2-. can be converted to other oxygen radical species, such as the hydroxyl radical (.OH), an extremely powerful oxidant capable of cleaving DNA, oxidizing protein, and initiating lipid peroxidation. Under many conditions, lipid peroxidation appears not to be initiated by .OH, but rather by an iron-oxygen complex. Regardless of the identity of the initiating species, transition metals are required for most of the deleterious reactions of oxygen. Superoxide and certain organic radicals have been found to release iron from ferritin.

Language of Publication

English

Unique Identifier

86293892

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Menu Position #10

MeSH Heading (Major)

Air Pollutants, Environmental|*PO; Free Radicals|*

MeSH Heading

Carbon Tetrachloride|ME; Chemistry; Human; Iron|ME; Lipid Peroxides|ME; Mixed Function Oxidases|ME; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0196-0644

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.13.12. (Mixed Function Oxidases); 0 (Air Pollutants, Environmental); 0 (Free Radicals); 0 (Lipid Peroxides); 56-23-5 (Carbon Tetrachloride); 7439-89-6 (Iron)

Record 14 from database: MEDLINE
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Title

Heavy metals and human spermatozoa. III. The toxicity of copper ions for spermatozoa.

Author

Holland MK; White IG

Address

Department of Veterinary Physiology, University of Sydney, NSW, Australia.

Source

Contraception, 1988 Dec, 38:6, 685-95

Abstract

The dissolution of copper ions from copper metal into a saline medium in vitro was quantified using a colourimetric assay. The presence of spermatozoa enhanced this dissolution and increasing the protein content of the medium further increased the rate of dissolution. Approximately 17% of the copper released was either tightly bound to the spermatozoa or was within the cell and could not be removed by repeated washing. Once spermatozoa were immobilized, they could not be revived by washing and repeated changes of medium, by addition of copper specific-chelating agent or by extensive dialysis. When the toxicity to spermatozoa of cuprous and cupric ions was compared with copper metal, it could be shown that the quantity of cupric ions required (0.2-0.4 mg/ml) was in excess of the total quantity of copper released into solution. The quantity of cuprous ion required (0.08-0.16 mg/ml) to exert similar toxic effects to copper, was within the range of copper released from the metal. Under the conditions of this study, it is possible that cuprous ion would be oxidised to the cupric form generating free radicals in the process. It is not known whether the toxic effect is due to the cuprous ion, per se, or to radicals generated in its oxidation. Increasing the protein content of the medium to levels similar to low (8 mg/ml) and high (64 mg/ml) values reported in human uterine fluid increased the dissolution rate of copper but also offered some protection against the toxic effects of copper metal and cuprous and cupric ions.

Language of Publication

English

Unique Identifier

89120117

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Menu Position #10

MeSH Heading (Major)

Copper|*TO; Spermatozoa|*DE

MeSH Heading

Human; Male; Serum Albumin|PD; Sperm Motility|DE; Spermatocidal Agents|PD; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0010-7824

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Serum Albumin); 7440-50-8 (Copper)

Record 15 from database: MEDLINE
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Title

Therapeutic iron chelators and their potential side-effects.

Author

Singh S; Khodr H; Taylor MI; Hider RC

Address

Department of Pharmacy, King's College, University of London, U.K.

Source

Biochem Soc Symp, 1995, 61:, 127-37

Abstract

A number of iron-chelating agents are currently being considered as orally active alternatives to desferrioxamine (DFO), the therapeutic agent for the treatment of body iron overload that is available at present. These include bidentate hydroxypyridinones (HPO), tridentate desferrithiocin (DFT) analogues and hexadentate aminocarboxylate (HBED) chelators. All chelating agents have the potential to induce toxic effects when iron homoeostasis is affected within the body. This can arise when the absorption, distribution and utilization of iron is affected. Alternatively, chelating agents can induce toxicity by directly interfering with iron-dependent metalloenzymes located within the body. These effects are, however, mainly localized to non-haem enzymes such as ribonucleotide reductase and lipoxygenase. The resultant iron complexes also have the ability to induce toxicity. Depending on the coordination geometry and donor atoms associated with the metal centre, redox cycling of the iron centre with the corresponding generation of free radicals can result.

Language of Publication

English

Unique Identifier

96232729

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Menu Position #10

MeSH Heading (Major)

beta-Thalassemia|*DT; Iron Chelating Agents|AD/AE/*TU

MeSH Heading

Administration, Oral; Human; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0067-8694

Country of Publication

ENGLAND

Record 16 from database: MEDLINE
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Title

Heterogeneous effect of flavonoids on K+ loss and lipid peroxidation induced by oxygen-free radicals in human red cells.

Author

Maridonneau-Parini I; Braquet P; Garay RP

Address

Source

Pharmacol Res Commun, 1986 Jan, 18:1, 61-72

Abstract

Treatment of fresh erythrocytes with phenazine methosulfate, an intracellular generator of oxygen-free radicals, and diethyldithiocarbamate an inhibitor of superoxide dismutase results in membrane damage consisting in lipid peroxidation and increase in passive K+ permeability. Various flavonoids which have previously been reported to act as oxygen-free radical scavengers were tested on this erythrocyte model. Surprisingly, flavonoids did not exhibit the same effect on the oxygen free radical-stimulated K+ permeability. It was possible to classify these agents into four groups: protective (those decreasing the oxygen-free radical-stimulated K+ permeability): kaempferol, naringenin, apigenin, naringin; toxic (those increasing the deleterious effect of oxygen-free radicals): myricetin, delphinidin, quercetin; biphasic effective (characterized by opposite effects depending on the concentration): phloretin, cyanin, catechin, morin and inactive: rutin, phloridzin. In addition, a similar classification was observed when membrane lipid peroxidation was examined, i.e. kaempferol decreased lipid peroxide formation whereas myricetin enhanced it, morin exhibited a biphasic effect and rutin has no effect. The previously reported metal chelating effect of flavonoids could not totally explain the protective effect of kaempferol as was demonstrated by the partial protective effect exhibited by desferrioxamine. Moreover, this study suggests that a generation of oxygen-free radicals in red cells induced a K+ loss which probably results from membrane lipid peroxidation.

Language of Publication

English

Unique Identifier

86149588

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MeSH Heading (Major)

Bioflavonoids|*PD; Erythrocytes|DE/*ME; Lipid Peroxides|*BL; Potassium|*BL

MeSH Heading

Cell Membrane Permeability; Deferoxamine|PD; Ditiocarb|PD; Free Radicals; Human; In Vitro; Malondialdehyde|BL; Superoxide Dismutase|BL

Publication Type

JOURNAL ARTICLE

ISSN

0031-6989

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.15.1.1 (Superoxide Dismutase); 0 (Bioflavonoids); 0 (Free Radicals); 0 (Lipid Peroxides); 147-84-2 (Ditiocarb); 542-78-9 (Malondialdehyde); 70-51-9 (Deferoxamine); 7440-09-7 (Potassium)

Record 17 from database: MEDLINE
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Title

Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.

Author

Juckett MB; Balla J; Balla G; Jessurun J; Jacob HS; Vercellotti GM

Address

Department of Medicine, University of Minnesota, Minneapolis, USA.

Source

Am J Pathol, 1995 Sep, 147:3, 782-9

Abstract

Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As were previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron-containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavy chain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examined human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue-detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo.

Language of Publication

English

Unique Identifier

95407677

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MeSH Heading (Major)

Endothelium, Vascular|CY/*DE; Ferritin|ME/*PD; Lipoproteins, LDL|AI/ME/*PD

MeSH Heading

Animal; Apoferritin|PD; Arteries; Cells, Cultured; Ceruloplasmin|ME; Coronary Arteriosclerosis|ME; Coronary Vessels|ME; Human; Immunoenzyme Techniques; Oxidation-Reduction; Swine

Publication Type

JOURNAL ARTICLE

ISSN

0002-9440

Country of Publication

UNITED STATES

Record 18 from database: MEDLINE
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Title

Surface reactivity in the pathogenic response to particulates.

Author

Fubini B

Address

UniversitÄa di Torino, FacoltÄa di Farmacia, Dipartimento di Chimica Inorganica, Italy. fubini@silver.ch.unito.it

Source

Environ Health Perspect, 1997 Sep, 105 Suppl 5:, 1013-20

Abstract

The peculiar characteristics of dust toxicity are discussed in relation to the processes taking place at the particle-biological medium interface. Because of surface reactivity, toxicity of solids is not merely predictable from chemical composition and molecular structure, as with water soluble compounds. With particles having the same bulk composition, micromorphology (the thermal and mechanical history of dust and adsorption from the environment) determines the kind and abundance of active surface sites, thus modulating reactivity toward cells and tissues. The quantitative evaluation of doses is discussed in comparisons of dose-response relationships obtained with different materials. Responses related to the surface of the particle are better compared on a per-unit surface than per-unit weight basis. The role of micromorphology, hydrophilicity, and reactive surface cations in determining the pathogenicity of inhaled particles is described with reference to silica and asbestos toxicity. Heating crystalline silica decreases hydrophilicity, with consequent modifications in membranolytic potential, retention, and transport. Transition metal ions exposed at the surface generate free radicals in aqueous suspensions. Continuous redox cycling of iron, with consequent activation-reactivation of the surface sites releasing free radicals, could account for the long-term pathogenicity caused by the inhalation of iron-containing fibers. In various pathogenicities caused by mixed dusts, the contact between components modifies toxicity. Hard metal lung disease is caused by exposure to mixtures of metals and carbides, typically cobalt (Co) and tungsten carbide (WC), but not to single components. Toxicity stems from reactive oxygen species generation in a mechanism involving both Co metal and WC in mutual contact. A relationship between the extent of water adsorption and biopersistence is proposed for vitreous fibers. Modifications of the surface taking place in vivo are described for ferruginous bodies and for the progressive comminution of chrysotile asbestos fibers.

Language of Publication

English

Unique Identifier

98063460

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MeSH Heading (Major)

Mineral Fibers|AN/*TO

MeSH Heading

Animal; Chemistry, Physical; Dust|AE; Human; Support, Non-U.S. Gov't; Surface Properties

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0091-6765

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
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Title

Free radicals in toxicology.

Author

Aust SD; Chignell CF; Bray TM; Kalyanaraman B; Mason RP

Address

Biotechnology Center, Utah State University, Logan 84322.

Source

Toxicol Appl Pharmacol, 1993 Jun, 120:2, 168-78

Abstract

Free radicals are recognized more and more frequently as being involved in the mechanism of toxicity of chemicals. In some cases, the organic radicals are involved, but often oxygen radicals result from redox cycling chemicals. Free radicals are usually very reactive, which, in addition to causing toxicities, can make them difficult to detect. Electron spin resonance (ESR) techniques are frequently used, but generally the radicals must be trapped to form a more stable radical for detection. Quantitation is therefore often very difficult. Free radicals of many xenobiotics are formed during their metabolism by enzymes such as cytochrome P450 or peroxidases. In some cases, chemicals can redox cycle using reductases, such as cytochrome P450 reductase, which can catalyze one-electron reductions. Some redox cycling xenobiotics reduce molecular oxygen by one electron to generate superoxide. Superoxide can cause toxicities against which superoxide dismutase is protective. However, in the presence of transition metals such as iron, superoxide can generate the very reactive hydroxyl radical by the iron-catalyzed Haber-Weiss reaction. Iron is therefore normally tightly controlled by transport and storage proteins. Chemicals that can release iron from these proteins can be very toxic, causing lipid, protein, and nucleic acid oxidation. The oxidation of these species, such as a low-density lipoprotein, is generally protected by a complex antioxidant system involving glutathione and glutathione peroxidase, vitamin E, ascorbic acid, etc.

Language of Publication

English

Unique Identifier

93289584

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MeSH Heading (Major)

Toxicology|*MT; Xenobiotics|ME/*TO

MeSH Heading

Animal; Ferritin|ME; Free Radicals|ME/TO; Human; Iron|TO; Oxidation-Reduction; Skatole|ME/TO

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0041-008X

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Free Radicals); 0 (Xenobiotics); 7439-89-6 (Iron); 83-34-1 (Skatole); 9007-73-2 (Ferritin)

Record 20 from database: MEDLINE
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Title

Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity.

Author

Nordmann R; Ribière C; Rouach H

Address

Source

Enzyme, 1987, 37:1-2, 57-69

Abstract

Lipoperoxidation, a degradative process of membranous polyunsaturated fatty acids, has been suggested to represent an important mechanism in the pathogenesis of ethanol toxicity on the liver and possibly also on the brain. Catalysis by transition metals, especially iron, is involved in the biosynthesis of free radicals contributing to lipid peroxidation. Although the exact nature of the redox-active iron implicated in this catalysis is still unknown, it has been well established that lipid peroxidation can be prevented in vitro by iron chelators such as desferrioxamine. Deprivation of redox-active iron through desferrioxamine inhibits by about 50% the microsomal oxidation of ethanol in vitro and reduces very significantly in vivo the overall ethanol elimination rate in rats. Administration of desferrioxamine together with ethanol also reduces the ethanol-induced disturbances in the antioxidant defense mechanisms of the hepatocyte. It also reduces in mice both the severity of physical dependence on ethanol and lethality following the acute administration of a narcotic dose of ethanol. Chronic overloading of rats with iron results, on the opposite, in an increased rate of ethanol elimination, although alcohol dehydrogenase and catalase activities are reduced and cytochrome P-450 depleted in the liver of such iron-overloaded animals. The magnitude of the ethanol-induced increase in lipid peroxidation and decrease in the major membranous antioxidant, alpha-tocopherol, is exacerbated in iron-overloaded rats. Several disturbances of iron metabolism have been reported in human alcoholics. Their contribution to ethanol toxicity appears very likely in the case of hepatic siderosis associated with alcohol abuse. Ethanol could however disturb iron metabolism even in the absence of gross abnormalities of the total iron stores. It is suggested that ethanol intoxication could increase cellular redox-active iron, thus contributing to an enhanced steady-state concentration of reactive-free radicals. This oxidative stress would lead to lipoperoxidative damage and cellular injury.

Language of Publication

English

Unique Identifier

87190272

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MeSH Heading (Major)

Alcohol, Ethyl|*ME; Alcoholic Intoxication|*ME; Iron|*ME

MeSH Heading

Animal; Brain|DE; Catalase|ME; Deferoxamine|PD; Free Radicals; Human; Hydroxides; Lipid Peroxides|ME; Liver|DE/EN; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0013-9432

Country of Publication

SWITZERLAND

CAS Registry/EC Number

EC 1.11.1.6 (Catalase); 0 (Free Radicals); 0 (Hydroxides); 0 (Lipid Peroxides); 3352-57-6 (Hydroxyl Radical); 64-17-5 (Alcohol, Ethyl); 70-51-9 (Deferoxamine); 7439-89-6 (Iron)

Record 21 from database: MEDLINE
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Title

Oxidative modification of low density lipoprotein (LDL) by activated human monocytes and the cell lines U937 and HL60.

Author

Cathcart MK; Chisolm GM 3d; McNally AK; Morel DW

Address

Department of Immunology and Cancer, Research Institute of the Cleveland Clinic Foundation, Ohio 44106.

Source

In Vitro Cell Dev Biol, 1988 Oct, 24:10, 1001-8

Abstract

Human peripheral blood monocytes, upon activation, have the capacity to oxidize low density lipoprotein (LDL) and render the LDL toxic to cultured cells. Previous studies by our laboratory indicate that this process is mediated by free radicals in that it can be prevented by addition of free radical scavengers and antioxidants during the incubation of monocytes with LDL. Here we report that optimal modification of LDL by monocytes was influenced by media composition. In the absence of added metal ions, oxidation was distinctly dependent on the concentration of monocytes as well as LDL concentration. Exposure of monocytes to lipopolysaccharide or stimulation of phagocytosis by opsonized zymosan resulted in marked enhancement of LDL oxidation compared to other activating agents. After exposure to activated monocytes, lipid oxidation products in the supernatant were found both in a high molecular weight fraction containing LDL (greater than 30,000 Daltons) and in a lipoprotein-free, low molecular weight fraction (less than 30,000 Daltons), yet only the high molecular weight, LDL-containing fraction was toxic to target cells. In addition, human myelomonocytic cell lines U937 and HL60 were shown to mediate oxidation of LDL. As with monocytes, exposing these cells to opsonized zymosan caused the level of LDL oxidation to be significantly enhanced. These findings offer further insight into the mechanisms of monocyte-mediated oxidation of lipoproteins and will facilitate studies investigating the role of monocyte-modified LDL in tissue injury.

Language of Publication

English

Unique Identifier

89033610

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MeSH Heading (Major)

Lipoproteins, LDL|*ME; Monocytes|*ME; Tumor Cells, Cultured|*ME

MeSH Heading

Culture Media; Human; In Vitro; Oxidation-Reduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0883-8364

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Culture Media)

Record 22 from database: MEDLINE
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Title

Structural damage to lymphocyte nuclei by H2O2 or gamma irradiation is dependent on the mechanism of OH. radical production.

Author

Allan IM; Vaughan AT; Milner AE; Lunec J; Bacon PA

Address

Department of Rheumatology, Medical School, University of Birmingham, UK.

Source

Br J Cancer, 1988 Jul, 58:1, 34-7

Abstract

Normal human lymphocytes were exposed to OH. radicals produced indirectly by exposure to H2O2 or directly by gamma irradiation. Using a flow cytometry technique to measure changes in nucleoid size, it was found that generation of OH. in each system produced a characteristic relaxation in nuclear supercoiling. Exposure of cells to H2O2 produced a metal-dependent step-wise relaxation in extracted nucleoids, while gamma irradiation induced a gradual dose-dependent increase in nucleoid size. The site-specific metal-dependent changes produced in lymphocytes incubated in H2O2 should also occur in gamma irradiated cells, but the characteristic effects on nuclear supercoiling would not be detected within the background of random DNA damage. The importance of metals in maintaining the supercoiled loop configuration of DNA within the protein matrix suggests that free radical damage at metal locations may be particularly toxic for the cell.

Language of Publication

English

Unique Identifier

89000461

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MeSH Heading (Major)

Hydrogen Peroxide|*PD; Hydroxides|*ME; Lymphocytes|DE/ME/*RE

MeSH Heading

Adult; Cell Nucleus|DE/RE; Deferoxamine|PD; Dose-Response Relationship, Radiation; DNA|DE/RE; Free Radicals; Gamma Rays; Human; Scattering, Radiation

Publication Type

JOURNAL ARTICLE

ISSN

0007-0920

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Free Radicals); 0 (Hydroxides); 70-51-9 (Deferoxamine); 7722-84-1 (Hydrogen Peroxide); 9007-49-2 (DNA)

Record 23 from database: MEDLINE
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Title

Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences [published erratum appears in Free Radic Biol Med 1991;10(3-4):249]

Author

Stadtman ER

Address

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

Source

Free Radic Biol Med, 1990, 9:4, 315-25

Abstract

In the presence of O2, Fe(III) or Cu(II), and an appropriate electron donor, a number of enzymic and nonenzymic oxygen free radical-generating systems are able to catalyze the oxidative modification of proteins. Whereas random, global modification of many different amino acid residues and extensive fragmentation occurs when proteins are exposed to oxygen radicals produced by high energy radiation, only one or a few amino acid residues are modified and relatively little peptide bond cleavage occurs when proteins are exposed to metal-catalyzed oxidation (MCO) systems. The available evidence indicates that the MCO systems catalyze the reduction of Fe(III) to Fe(II) and of O2 to H2O2 and that these products react at metal-binding sites on the protein to produce active oxygen (free radical?) species (viz; OH, ferryl ion) which attack the side chains of amino acid residues at the metal-binding site. Among other modifications, carbonyl derivatives of some amino acid residues are formed; prolyl and arginyl residues are converted to glutamylsemialdehyde residues, lysyl residues are likely converted to 2-amino-adipylsemialdehyde residues; histidyl residues are converted to asparagine and/or aspartyl residues; prolyl residues are converted to glutamyl or pyroglutamyl residues; methionyl residues are converted to methionylsulfoxide residues; and cysteinyl residues to mixed-disulfide derivatives. The biological significance of these metal ion-catalyzed reactions is highlighted by the demonstration: (i) that oxidative modification of proteins "marks" them for degradation by most common proteases and especially by the cytosolic multicatalytic proteinase from mammalian cells; (ii) protein oxidation contributes substantially to the intracellular pool of catalytically inactive and less active, thermolabile forms of enzymes which accumulate in cells during aging, oxidative stress, and in various pathological states, including premature aging diseases (progeria, Werner's syndrome), muscular dystrophy, rheumatoid arthritis, cataractogenesis, chronic alcohol toxicity, pulmonary emphysema, and during tissue injury provoked by ischemia-reperfusion. Furthermore, the metal ion-catalyzed protein oxidation is the basis of biological mechanisms for regulating changes in enzyme levels in response to shifts from anaerobic to aerobic metabolism, and probably from one nutritional state to another. It is also involved in the killing of bacteria by neutrophils and in the loss of neutrophil function following repeated cycles of respiratory burst activity.

Language of Publication

English

Unique Identifier

91131022

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MeSH Heading (Major)

Copper|*ME; Ferrous Compounds|*ME; Oxygen|*ME; Proteins|*ME

MeSH Heading

Aging; Animal; Free Radicals; Human; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0891-5849

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Ferrous Compounds); 0 (Free Radicals); 7440-50-8 (Copper); 7782-44-7 (Oxygen)

Record 24 from database: MEDLINE
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Title

Role of oxygen free radicals in carcinogenesis and brain ischemia.

Author

Floyd RA

Address

Molecular Toxicology Research Group, Oklahoma Medical Research Foundation, Oklahoma City 73104.

Source

FASEB J, 1990 Jun, 4:9, 2587-97

Abstract

Even though oxygen is necessary for aerobic life, it can also participate in potentially toxic reactions involving oxygen free radicals and transition metals such as Fe that damage membranes, proteins, and nucleic acids. Oxygen free radical reactions and oxidative damage are in most cases held in check by antioxidant defense mechanisms, but where an excessive amount of oxygen free radicals are produced or defense mechanisms are impaired, oxidative damage may occur and this appears to be important in contributing to several pathological conditions including aging, carcinogenesis, and stroke. Several newer methods, such as in vivo spin-trapping, have become available to monitor oxygen free radical flux and quantitate oxidative damage. Using a combination of these newer methods collectively focused on one model, recent results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage-induced loss of glutamine synthetase activity, may be a key event in stroke-induced brain injury. Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8-hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin-traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions.

Language of Publication

English

Unique Identifier

90269543

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MeSH Heading (Major)

Carcinogens|*/ME; Cerebral Ischemia|*CI; Free Radicals|*; Oxygen|*AE

MeSH Heading

Animal; Human; Lipid Peroxidation; Proteins|ME; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Carcinogens); 0 (Free Radicals); 7782-44-7 (Oxygen)

Record 25 from database: MEDLINE
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Title

Free radicals derived from oxygen, and medicine.

Author

Duracková Z; Bergendi L; Liptáková A; Muchová J

Address

Ustav lekárskej chémie, biochémie a klinickej biochémie LFUK, Bratislava, Slovakia.

Source

Bratisl Lek Listy, 1993 Aug, 94:8, 419-34

Abstract

Toxic free radicals may be produced by many reactions, which are necessary for the maintenance of normal metabolism, and the production of energy in cells. The origin, reactivity with other molecules and removal of free radicals, is in the foreground of interest since their effect is mostly toxic and result in a whole series of pathological states of cells, organs and whole organisms. Production of these radicals increases in oxidative stress and in the presence of ions of metals (chiefly iron), leads to the creation of more reactive metabolites. The generally accepted view is that the main biological actor in damaged tissues is the hydroxyl radical (OH), which is created in the iron catalyzed Haber-Weiss reaction. The balance between the increased creation of free radicals in various pathological states, or unfavourable conditions in the environment, and natural antioxidants of a low-molecular (vitamin C, E, glutathione etc.) or enzyme character (superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, etc.), plays the chief role in damage which is the cause of many diseases and ageing. (Fig. 3, Tab. 5, Ref. 62.).

Language of Publication

ENG LA=SLO

Unique Identifier

94272980

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MeSH Heading (Major)

Free Radicals|*/CH/ME

MeSH Heading

Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0006-9248

Country of Publication

SLOVAKIA

CAS Registry/EC Number

0 (Free Radicals)

Record 26 from database: MEDLINE
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Title

Radiation and aging: free radical damage, biological response and possible antioxidant intervention.

Author

Greenstock CL

Address

Radiation Biology Branch, AECL Research, Chalk River, Ontario, Canada.

Source

Med Hypotheses, 1993 Nov, 41:5, 473-82

Abstract

In this review, the basic processes responsible for radiation-induced changes in critical cell components and their biological consequences will be discussed. The chemical and physical alterations in biomolecules are mediated by free radicals and other reactive intermediates formed, following absorption of radiant energy, by ionization of proximal targets or the surrounding water molecules. Accumulation of free radical damage and its catalysis by various oxidants including quinones and other age pigments, metal ions, lipid peroxides, prostaglandins and components released from cells, increase with age. A cell's response to such damage depends upon environmental and inherited factors. DNA repair is an effective way to protect against radiation damage, but other constitutive or inducible defence mechanisms can also modify biological response, and these processes generally become less effective with age. Loss of fidelity with age of bio-feedback mechanisms including homeostasis, redox control, ion and metabolic regulation, which in turn affects cell growth and differentiation, energy efficiency, the immune system and general health, can be associated with free radical pathology. Current theories of aging will be examined including those involving wear-and-tear, genetic, metabolic, immunologic and biochemical factors. Ionizing radiation, as with other external stresses including UV, heat, chemotherapeutic agents, chemical carcinogens and tumor promoters, interact with nucleic acids, proteins and membrane phospholipids facilitating free radical-mediated oxidative damage. Appropriate antioxidant intervention, by inhibiting or reducing free radical toxicity, may offer protection against radiation, and alleviate or delay symptoms of aging and chronic disease.

Language of Publication

English

Unique Identifier

94195133

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MeSH Heading (Major)

Aging|DE/ME/*RE

MeSH Heading

Animal; Antioxidants|PD; DNA Damage; Free Radicals; Human; Models, Biological; Radiation Injuries|ET/ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0306-9877

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Antioxidants); 0 (Free Radicals)

Record 27 from database: MEDLINE
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Title

Reductive metabolism of nitroprusside in rat hepatocytes and human erythrocytes.

Author

Rao DN; Elguindi S; O'Brien PJ

Address

Faculty of Pharmacy, University of Toronto, Canada.

Source

Arch Biochem Biophys, 1991 Apr, 286:1, 30-7

Abstract

The metabolism of nitroprusside by hepatocytes or subcellular fractions involves a one-electron reduction of nitroprusside to the corresponding metal-nitroxyl radical. Thiol compounds also reduced nitroprusside to the metal-nitroxyl radical apparently via a thiol adduct. The nitroprusside reduction by microsomes was shown to be due to cytochrome P450 reductase as an antibody to cytochrome P450 reductase inhibits the microsomal reduction of nitroprusside, and the inhibitors of cytochrome P450 such as carbon monoxide or metyrapone had no effect. The reduction of nitroprusside by mitochondria in the presence of NADH or NADPH also produced the metal-nitroxyl radical. In hepatocytes, both mitochondria and the cytochrome P450 reductase are involved in the reduction of nitroprusside. The reductive metabolism of nitroprusside was found to produce toxic by-products, namely, free cyanide anion and hydrogen peroxide. We have also detected thiyl radicals formed in the thiol compound reduction of NP. We propose that cyanide and hydrogen peroxide are important toxic species formed in the metabolism of nitroprusside. The rate of reductive metabolism of nitroprusside by rat hepatocytes was much higher than with human erythrocytes. Therefore the major site of nitroprusside metabolism in vivo may be liver and not blood as originally proposed.

Language of Publication

English

Unique Identifier

91378306

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MeSH Heading (Major)

Erythrocytes|*ME; Liver|*ME; Microsomes, Liver|*EN; Nitroprusside|*ME; NADPH-Ferrihemoprotein Reductase|*ME

MeSH Heading

Animal; Cells, Cultured; Comparative Study; Cytosol|ME; Electron Spin Resonance Spectroscopy; Free Radicals; Human; Kinetics; Male; Mitochondria, Liver|ME; Oxidation-Reduction; Rats; Rats, Inbred Strains

Publication Type

JOURNAL ARTICLE

ISSN

0003-9861

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); 0 (Free Radicals); 15078-28-1 (Nitroprusside)

Record 28 from database: MEDLINE
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Title

Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals.

Author

Okada S

Address

First Department of Pathology, Okayama University Medical School, Japan.

Source

Pathol Int, 1996 May, 46:5, 311-32

Abstract

Oxygen is poisonous, but we cannot live without it. The high oxidizing potential of oxygen molecules (dioxygen) is a valuable source of energy for the organism and its reactivity is low; that is, spin forbidden. However, the dioxygen itself is a 'free radical' and, especially in the presence of transition metals, it is a major promoter of radical reactions in the cell. Humans survive only by virtue of their elaborate defense mechanisms against oxygen toxicity. Iron is the most abundant transition metal in the human body. Because iron shows wide variation in redox potential with different co-ordination ligands, it may be used as a redox intermediate in many biological mechanism. However, it is precisely this redox activeness that makes iron a key participant in free radical production. The current research on the relationship between iron and cancer is briefly reviewed. Research results are reported here which indicate that iron, when bound to certain ligands, can cause free-radical mediated tissue damage and become carcinogenic. The present study also suggests that iron may also have a significant role in spontaneous human cancer.

Language of Publication

English

Unique Identifier

96405749

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MeSH Heading (Major)

Iron|*TO; Neoplasms|*CI; Reactive Oxygen Species|*

MeSH Heading

Animal; Disease Models, Animal; Free Radicals; Human; Neoplasms, Experimental|CI; Oxidation-Reduction; Oxygen|CH; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

1320-5463

Country of Publication

AUSTRALIA

Record 29 from database: MEDLINE
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Title

Active oxygen in neuromuscular disorders.

Author

Davison A; Tibbits G; Shi ZG; Moon J

Address

Faculty of Applied Sciences, School of Kinesiology, Simon Fraser University, Burnaby, Canada.

Source

Mol Cell Biochem, 1988 Dec, 84:2, 199-216

Abstract

Although muscle and nerve are reasonably well protected against active oxygen and related free radicals, environmental or inherited malfunctions can overpower their defences. Active oxygen is involved in many neuropathies and myopathies. In every case the damage is caused by agents which exert effects disproportionately greater than the quantities encountered, through a variety of amplification mechanisms. We can categorize these amplification mechanisms as follows: (a) non-replacement of targets (e.g. loss of genetic information, ataxia telangectasia being an hereditary ataxia in which an oxygen mediated chromosomal instability is apparent), (b) non-removal of unwanted materials (e.g. lipofuscin accumulation in brain and heart), (c) redox cycling, usually involving catalysis by trace-metal ions (e.g. some forms of Parkinsonism), (d) non-redox catalysis (e.g. toxicity in cardiac muscle or brain due to vanadium or aluminium respectively), (e) modification of ion transport (e.g. calcium ionophore or acrylamide induce histopathological changes in muscle, similar in some respects to those seen in Duchenne muscular dystrophy), (f) compromised defences (e.g. muscle and nerve become particularly susceptible to free radical damage after loss of the protective actions of vitamin E), and (g) amplification by inflammatory and immune responses (e.g. multiple sclerosis, reperfusion injury to brain and heart, and traumatic injury to nervous tissue). Unfortunately, a variety of therapeutic agents which might be expected to protect against almost every conceivable form of oxygen mediated damage have proved clinically ineffective in most of these disorders. The reasons for this will be explored with an emphasis on common features, differences, mechanisms, and potential therapeutic approaches.

Language of Publication

English

Unique Identifier

89159172

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MeSH Heading (Major)

Neuromuscular Diseases|*PP; Oxygen|*PH

MeSH Heading

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

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0300-8177

Country of Publication

NETHERLANDS

CAS Registry/EC Number

7782-44-7 (Oxygen)

Record 30 from database: MEDLINE
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Title

Oxygen free radicals in nephrology.

Author

Canavese C; Stratta P; Vercellone A

Address

Department of Nephrology, University of Torino, Italia.

Source

Int J Artif Organs, 1987 Nov, 10:6, 379-89

Abstract

For living creatures with an aerobic metabolism, the univalent reduction of oxygen can lead to formation within the cell of intermediate products with marked chemical instability and strong potential toxicity. These are the free radicals (FR) superoxide and hydroxyl, hydrogen peroxide and the singlet 1O2. Their toxicity is primarily expressed through the peroxidation of membrane lipids, resulting in mitochondrial, lysosomal and parietal damage. It is enhanced by the presence of metals in trace amounts. Imbalance between the production of FR and the availability of FR scavengers (superoxide dismutase, catalase, glutathione peroxidase, etc.) may underlie different human pathologies. FR have been thought to play a part in inflammation, the aging process, carcinomatous transformations, damage due to recirculation and autoimmune diseases. As far as the kidney is concerned, the intervention of FR has been demonstrated or can be postulated in various contexts in the light of what has been observed in other pathologies: immunological nephritis, toxic nephropathies, microthrombotic and microangiopathic processes, damage caused by post-ischemic reflow, and problems in the preservation and rejection of transplants. FR have also been incriminated in lung lesions following intradialytic leukostasis and some aspects of toxicity ascribable to uremia. Subject to the precautions imposed by the need for theoretical, experimental and clinical verification, FR biochemistry offers new keys to the interpretation of a variety of kidney pathologies and opens up new prospects for treatment, both through a better understanding of the mechanism of action of drugs already known and employed, and with regard to the practical possibility of using alternative or combined forms of therapy.

Language of Publication

English

Unique Identifier

88168928

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MeSH Heading (Major)

Kidney Diseases|*ME; Oxygen|*ME/PH

MeSH Heading

Animal; Free Radicals; Human; Oxidation-Reduction

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0391-3988

Country of Publication

ITALY

CAS Registry/EC Number

0 (Free Radicals); 7782-44-7 (Oxygen)

Record 31 from database: MEDLINE
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Title

Reactive oxygen species and Alzheimer's disease.

Author

Multhaup G; Ruppert T; Schlicksupp A; Hesse L; Beher D; Masters CL; Beyreuther K

Address

ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany. g.multhaup@mail.zmbh.uni-heidelberg.de

Source

Biochem Pharmacol, 1997 Sep, 54:5, 533-9

Abstract

Although a consensus that Alzheimer's disease (AD) is a single disease has not been reached yet, the involvement of the amyloid precursor protein (APP) and betaA4 (A beta) in the pathologic changes advances our understanding of the underlying molecular alterations. Increasing evidence implicates oxidative stress in the neurodegenerative process of AD. This hypothesis is based on the toxicity of betaA4 in cell cultures, and the findings that aggregation of betaA4 can be induced by metal-catalyzed oxidation and that free oxygen radicals may be involved in APP metabolism. Another neurological disorder, familial amyotrophic lateral sclerosis (FALS), supports our view that AD and FALS may be linked through a common mechanism. In FALS, SOD-Cu(I) complexes are affected by hydrogen peroxide and free radicals are produced. In AD, the reduction of Cu(II) to Cu(I) by APP involves an electron-transfer reaction and could also lead to a production of hydroxyl radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I) complexes may contribute to neurodegeneration in AD.

Language of Publication

English

Unique Identifier

97477005

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MeSH Heading (Major)

Alzheimer Disease|GE/*ME/PA; Amyloid beta-Protein|*ME; Amyloid beta-Protein Precursor|*ME; Reactive Oxygen Species|*

MeSH Heading

Aging; Amyotrophic Lateral Sclerosis|ME/PA; Brain|ME/PA; Human; Oxidative Stress; Superoxide Dismutase|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0006-2952

Country of Publication

ENGLAND

Record 32 from database: MEDLINE
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Title

Amyloid precursor protein, copper and Alzheimer's disease.

Author

Multhaup G

Address

ZMBH Center for Molecular Biology, University of Heidelberg, Germany.

Source

Biomed Pharmacother, 1997, 51:3, 105-11

Abstract

Although a consensus that Alzheimer's disease (AD) is a single disease has not yet been reached, the involvement of the amyloid precursor protein (APP) and beta A4 (A beta) in the pathologic changes advances our understanding of the underlying molecular alterations. Increasing evidence implicates oxidative stress in the neurodegenerative process of AD. This hypothesis is based on the toxicity of beta A4 in cell cultures, and the findings that aggregation of beta A4 can be induced by metal-catalyzed oxidation and that free oxygen radicals might be involved in APP metabolism. Another neurological disorder, familial amyotrophic lateral sclerosis (FALS), supports our view that AD and FALS might be linked through a common mechanism. In FALS, SOD-Cu(I) complexes are affected by hydrogen peroxide and free radicals are produced. In AD, the reduction of Cu(II) to Cu(I) by APP involves an electron-transfer reaction and could also lead to a production of hydroxyl radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I) complexes may contribute to neurodegeneration in AD.

Language of Publication

English

Unique Identifier

97324976

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MeSH Heading (Major)

Alzheimer Disease|*ME; Amyloid beta-Protein Precursor|*ME; Copper|*ME

MeSH Heading

Amyotrophic Lateral Sclerosis|GE/ME; Human; Hydroxyl Radical|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0753-3322

Country of Publication

FRANCE

Record 33 from database: MEDLINE
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Title

Oxidative stress: a role in the pathogenesis of Parkinson's disease.

Author

Götz ME; Freyberger A; Riederer P

Address

Klinische Neurochemie, Universitäts-Nervenklinik Würzburg, Federal Republic of Germany.

Source

J Neural Transm Suppl, 1990, 29:, 241-9

Abstract

The degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson's disease (PD). However, the etiology of this degeneration is not known. Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease. An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper. The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN). Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD.

Language of Publication

English

Unique Identifier

90293750

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MeSH Heading (Major)

Brain|*ME/PP; Dopamine|*ME; Melanins|*ME; Monoamine Oxidase|*ME; Parkinson Disease|*ME/PP

MeSH Heading

Aged; Aged, 80 and over; Glutathione|ME; Human; Middle Age

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0303-6995

Country of Publication

AUSTRIA

CAS Registry/EC Number

EC 1.4.3.4 (Monoamine Oxidase); 0 (Melanins); 51-61-6 (Dopamine); 70-18-8 (Glutathione)

Record 34 from database: MEDLINE
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Title

Effects of phytic acid on the myoglobin-t-butylhydroperoxide-catalysed oxidation of uric acid and peroxidation of erythrocyte membrane lipids.

Author

Ko KM; Godin DV

Address

Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Source

Mol Cell Biochem, 1991 Feb 27, 101:1, 23-9

Abstract

Phytic acid stimulated the myoglobin-t-butylhydroperoxide (TBHP)-catalysed oxidation of uric acid, but inhibited the peroxidation of erythrocyte membrane lipids induced by the same system. Butylated hydroxytoluene, a free radical chain reaction-terminating antioxidant, also suppressed the myoglobin-TBHP-induced lipid peroxidation. Moreover, phytic acid inhibited the hydroxyl radical-induced degradation of deoxyribose, but the extent of inhibition in this system was reduced by increasing the ferric ion concentration, suggesting that these effects of phytic acid on the myoglobin-TBHP-mediated oxidation are more likely attributable to its metal chelating properties rather than to a free radical scavenging action. The effectiveness of phytic acid, a naturally occurring antioxidant, in the inhibition of both iron- (as previously shown) and myoglobin-dependent lipid peroxidation suggests its possible therapeutic application as a non-toxic antioxidant for ameliorating the extent of oxy-radical-mediated myocardial ischemia/reperfusion damage.

Language of Publication

English

Unique Identifier

91186975

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MeSH Heading (Major)

Erythrocyte Membrane|*DE/ME; Membrane Lipids|*ME; Myoglobin|*PH; Peroxides|CH/*PD; Phytic Acid|*PD; Uric Acid|*ME

MeSH Heading

Human; In Vitro; Lipid Peroxidation; Oxidation-Reduction; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0300-8177

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Membrane Lipids); 0 (Myoglobin); 0 (Peroxides); 69-93-2 (Uric Acid); 75-91-2 (tert-butylhydroperoxide); 83-86-3 (Phytic Acid)

Record 35 from database: MEDLINE
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Title

Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics.

Author

Dorr RT

Address

Department of Internal Medicine and Pharmacology, University of Arizona, College of Medicine, Tucson.

Source

Semin Oncol, 1992 Apr, 19:2 Suppl 5, 3-8

Abstract

Bleomycin is a glycopeptide antibiotic with a unique mechanism of antitumor activity. The drug binds to guanosine-cytosine-rich portions of DNA via association of the "S" tripeptide and by partial intercalation of the bithiazole rings. A group of five nitrogen atoms arranged in a square-pyramidal conformation binds divalent metals including iron, the active ligand, and copper, an inactive ligand. Molecular oxygen, bound by the iron, can produce highly reactive free radicals and Fe(III). The free radicals produce DNA single-strand breaks at 3'-4' bonds in deoxyribose. This yields free base propenals, especially of thymine: cytotoxicity is cell-cycle-phase specific for G2 phase. In humans, bleomycin is rapidly eliminated primarily by renal excretion. This accounts for approximately half of a dose. In patients with renal compromise or extensive prior cisplatin therapy, the drug half-life can extend from 2 to 4 hours up to 21 hours. Thus, dose adjustments are needed when creatinine clearance is less than or equal to 3N mL/min. Finally, resistance to bleomycin in normal tissues can be correlated with the presence of a bleomycin hydrolase enzyme, which is in the cysteine proteinase family. The enzyme replaces a terminal amine with a hydroxyl, thereby inhibiting iron binding and cytotoxic activity. The low concentration of enzyme in the skin and lung may explain the unique sensitivity of these tissues to bleomycin toxicity. However, correlation of hydrolase levels with tumor cell sensitivity has thus far been negative.

Language of Publication

English

Unique Identifier

93030884

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MeSH Heading (Major)

Bleomycin|AI/CH/*PD/PK

MeSH Heading

Glycoside Hydrolases|PD; Human; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0093-7754

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 3.2.1. (Glycoside Hydrolases); EC 3.4.22.- (bleomycin hydrolase); 11056-06-7 (Bleomycin)

Record 36 from database: MEDLINE
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Title

Antiproliferative and DNA-scission activities of L-ascorbic acid in the presence of copper chelates.

Author

Chiou SH; Ohtsu N

Address

Source

Proc Natl Sci Counc Repub China [B], 1985 Oct, 9:4, 275-80

Abstract

L-Ascorbic acid inhibits the growth of mouse neuroblastoma and human endometrial carcinoma cells at concentrations greater than 100 microM. Under the same concentrations used in cell culture study, normal human lung fibroblasts show less sensitivity to the antiproliferative effect of ascorbate than tumor cell lines. The antitumor activity of ascorbate can be greatly potentiated by the combination with copper ions or copper chelates. The exposure of normal and tumor cells to the mixtures of ascorbate and copper chelates, especially Cu2+-o-phenanthroline and Cu2+-2,9-dimethyl-o-phenanthroline complexes, resulted in the killing of a large proportion of cell populations whereas the organic ligand portion of metal complexes was much less toxic. These copper chelates in combination with ascorbate showed different degrees of DNA-scission activities which could not be correlated with their cytotoxicities in the cell culture study. It is suggested that the primary targets of these antiproliferative agents may be on the biological sites such as cell membrane other than DNA in the nucleus which has been commonly assumed as the critical target for most free radical-generating antitumor drugs.

Language of Publication

English

Unique Identifier

86149972

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MeSH Heading (Major)

Ascorbic Acid|*PD; Cell Division|*DE; DNA, Viral|*ME

MeSH Heading

Animal; Bacteriophage lambda; Cell Line; Chelating Agents|PD; Copper|PD; Female; Human; Kinetics; Lung; Mice; Neuroblastoma; Support, Non-U.S. Gov't; Uterine Neoplasms

Publication Type

JOURNAL ARTICLE

ISSN

0253-8415

Country of Publication

TAIWAN

CAS Registry/EC Number

0 (Chelating Agents); 0 (DNA, Viral); 50-81-7 (Ascorbic Acid); 7440-50-8 (Copper)

Record 37 from database: MEDLINE
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Title

Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents.

Author

Lohrer H; Robson T

Address

Cancer Research Unit, University of Newcastle upon Tyne, Medical School, UK.

Source

Carcinogenesis, 1989 Dec, 10:12, 2279-84

Abstract

Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cdr), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-N'-nitro-N'-nitrosoguan idine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals.

Language of Publication

English

Unique Identifier

90075328

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MeSH Heading (Major)

Alkylating Agents|*PD; Metallothionein|BI/*GE/PH

MeSH Heading

Animal; Bleomycin|PD; Cadmium|PD; Cell Line; Cell Survival|DE/RE; Cobalt Radioisotopes; Cricetulus; Drug Resistance; Female; Gamma Rays; Gene Expression; Genes, Structural; Hamsters; Human; Methylnitronitrosoguanidine|PD; Mitomycins|PD; Ovary; Support, Non-U.S. Gov't; Transfection; Zinc|PD

Publication Type

JOURNAL ARTICLE

ISSN

0143-3334

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Alkylating Agents); 0 (Cobalt Radioisotopes); 0 (Mitomycins); 11056-06-7 (Bleomycin); 50-07-7 (Mitomycin C); 70-25-7 (Methylnitronitrosoguanidine); 7440-43-9 (Cadmium); 7440-66-6 (Zinc); 9038-94-2 (Metallothionein)

Record 38 from database: MEDLINE
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Title

Interactions of manganese with human brain glutathione-S-transferase.

Author

Vescovi A; Gebbia M; Cappelletti G; Parati EA; Santagostino A

Address

Lab. of Neuropharmacology, Neurological Institute C. Besta, Milan, Italy.

Source

Toxicology, 1989 Jul 17, 57:2, 183-91

Abstract

Chronic exposure to manganese-laden dusts induces, in humans and lower primates, neurological disorders with clinicopathological features that resemble idiopathic Parkinson's disease. As many authors have suggested, manganese neurotoxicity could be related to the capability of this metal to increase catechol autoxidation in catecholaminergic neurons, therefore increasing the formation of toxic compounds such as peroxides, superoxides, free radicals, and semi-orthoquinones. Oxidative stresses and consequent neuronal damage could then occur if physiological scavenger mechanisms fail in their detoxifying action. We here report that manganese chloride weakly inhibits, in a dose-dependent way by a reversible competitive mechanism, human brain glutathione-S-transferases possibly suggesting that manganese intoxication could cause intraneuronal accumulation of cytotoxic compounds. We also report that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin known to induce in man Parkinson-like syndromes, and one of its metabolites 1-methyl-4-phenylpyridinium failed to decrease glutathione-S-transferase activity.

Language of Publication

English

Unique Identifier

89318229

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MeSH Heading (Major)

Brain|*EN; Glutathione Transferases|*ME; Manganese|*PD

MeSH Heading

Cytosol|EN; Human; Kinetics; Pyridines|PD; Pyridinium Compounds|PD; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0300-483X

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 2.5.1.18 (Glutathione Transferases); 0 (Pyridines); 0 (Pyridinium Compounds); 28289-54-5 (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine); 48134-75-4 (1-Methyl-4-phenylpyridinium); 7439-96-5 (Manganese); 7773-01-5 (manganese chloride)

Record 39 from database: MEDLINE
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Title

Adding Zn2+ induces DNA fragmentation and cell condensation in cultured human Chang liver cells.

Author

Paramanantham R; Sit KH; Bay BH

Address

Department of Anatomy, National University of Singapore, Kent Ridge, Singapore.

Source

Biol Trace Elem Res, 1997 Jul, 58:1-2, 135-47

Abstract

Zinc (Zn) is a trace element in human cells and regarded as an essential nutrient with established deficiency states affecting multiple organs in the body. However, it has been reported that Zn uptake is associated with some serious harmful effects, such as inhibition of DNA synthesis and enhanced toxicity from reactive oxygen species. We have previously shown that in vivo administration of Zn2+ in C57/6J mice induces weight loss and massive hair loss where the normal course hair becomes replaced by fine vello hair, simulating the side effects from cancer chemotherapy where oxidative free radical damage is implicated in association with DNA fragmentation and programmed cell death (PCD). Here, in vitro flow cytometric studies on human Chang liver showed Zn2+ causing cell condensation with DNA fragmentation that occurred in a dose-dependent manner, an effect replicated by micrococcal nuclease digestion. Specific terminal deoxynucleotidyl transferase-(TdT) mediated labeling of 3'-OH ends of DNA nicks corroborated the flow cytometric profiles of propidium iodide-DNA binding where degradation of both 2 and 4 N genomic DNA resulted in a solitary 1N peak presentation. DNA degradation concomitant with cell condensation is seen as an established hallmark of PCD. We further showed that Zn2+ could enhance the generation of hydroxyl free radicals (OH.) by the transition metal vanadium. Glutathione, the cell's main reducing agent, underwent corresponding reduction. The results suggested that Zn supplementation could induce features resembling PCD.

Language of Publication

English

Unique Identifier

98029755

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MeSH Heading (Major)

Apoptosis|*DE; Chlorides|*PD; DNA Fragmentation|*DE; Liver|CY/*DE; Oxidative Stress|*DE; Zinc Compounds|*PD

MeSH Heading

Cell Cycle|DE; Cells, Cultured; Culture Media, Serum-Free; Deoxyuracil Nucleotides|ME; DNA|AN; DNA Nucleotidylexotransferase|ME; Flow Cytometry; Glutathione|ME; Human; Hydroxyl Radical|ME; Micrococcal Nuclease|ME; Microscopy, Phase-Contrast; Support, Non-U.S. Gov't; Vanadates|PD

Publication Type

JOURNAL ARTICLE

ISSN

0163-4984

Country of Publication

UNITED STATES

Record 40 from database: MEDLINE
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Title

Liver copper storage and transport during development: implications for cytotoxicity.

Author

Luza SC; Speisky HC

Address

Biochemical Pharmacology and Lipids Unit, Nutrition and Food Technology Institute, University of Chile, Santiago.

Source

Am J Clin Nutr, 1996 May, 63:5, 812S-20S

Abstract

Copper is an essential trace element for many biological processes. Its functions range from influencing specific gene expression to serving as a cofactor or prosthetic group for several enzymes. Intakes of copper at doses that exceed physiologic demands are normally met with efficient homeostatic mechanisms. Ceruloplasmin, albumin, and transcuprein, and to a lesser extent certain amino acids, are major copper-transporting constituents in circulating plasma. After its hepatic uptake, copper may be stored within hepatocytes, secreted into plasma, or excreted in bile. The biliary route represents the major excretory pathway of copper and largely accounts for its hepatic turnover. Copper retained by hepatocytes is mostly bound to specific metal-binding proteins, primarily metallothionein, or incorporated into several cuproenzymes. Copper incorporation into metallothionein and certain cuproproteins appears to require prior binding of copper to glutathione, thus defining a relation between copper metabolism and the intracellular availability of glutathione. Hepatic metallothionein concentrations can be modulated by dietary copper; changes in metallothionein and in copper status are significant throughout development. Binding of copper to metallothionein provides a temporary storage for cytoplasmic copper, preventing it from occurring as (potentially toxic) free ionic metal. In its unbound form, copper can generate hydroxyl radicals. Because metallothionein exhibits a high reactivity toward these radicals, it is increasingly recognized to play a protective role against copper-induced cytotoxicity. We discuss some of the possible toxicologic implications that may arise from changes in hepatic copper and metallothionein status during development.

Language of Publication

English

Unique Identifier

96204963

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MeSH Heading (Major)

Copper|AN/*ME/TO; Liver|CH/*DE/*ME

MeSH Heading

Animal; Bile|ME; Biological Transport|PH; Ceruloplasmin|ME/PH; Glutathione|ME/PH; Human; Metallothionein|ME/PH

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9165

Country of Publication

UNITED STATES

Record 41 from database: MEDLINE
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Title

Can the mechanisms of aluminum neurotoxicity be integrated into a unified scheme?

Author

Strong MJ; Garruto RM; Joshi JG; Mundy WR; Shafer TJ

Address

Department of Clinical Neurological Sciences, University of Western Ontario, London, Canada. mstrong@julian.uwo.ca

Source

J Toxicol Environ Health, 1996 Aug, 48:6, 599-613

Abstract

Regardless of the host, the route of administration, or the speciation, aluminum is a potent neurotoxicant. In the young adult or developmentally mature host, the neuronal response to Al exposure can be dichotomized on morphological grounds. In one, intraneuronal neurofilamentous aggregates are formed, whereas in the other, significant neurochemical and neurophysiological perturbations are induced without neurofilamentous aggregate formation. Evidence is presented that the induction of neurofilamentous aggregates is a consequence of alterations in the posttranslational processing of neurofilament (NF), particularly with regard to phosphorylation state. Although Al has been reported to impact on gene expression, this does not appear to be critical to the induction of cytoskeletal pathology. In hosts responding to Al exposure without the induction of cytoskeletal pathology, impairments in glucose utilization, agonist-stimulated inositol phosphate accumulation, free radical-mediated cytotoxicity, lipid peroxidation, reduced cholinergic function, and altered protein phosphorylation have been described. The extent to which these neurochemical modifications correlate with the induction of a characteristic neurobehavioral state is unknown. In addition to these paradigms, Al is toxic in the immediate postnatal interval. Whether unique mechanisms of toxicity are involved during development remains to be determined. In this article, the mechanisms of Al neurotoxicity are reviewed and recommendations are put forth with regard to future research. Primary among these is the determination of the molecular site of Al toxicity, and whether this is based on Al substitution for divalent metals in a number of biological processes. Encompassed within this is the need to further understand the genesis of host- and developmental-specific responses.

Language of Publication

English

Unique Identifier

96368793

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MeSH Heading (Major)

Aluminum|*AE/PK; Central Nervous System|*DE/PP; Pregnancy, Animal|*DE

MeSH Heading

Adult; Animal; Cytoskeleton|DE/PA; Female; Fetal Development|DE; Gene Expression; Human; Metabolism|DE; Neurochemistry|MT; Neurophysiology|MT; Pregnancy; Research Design; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0098-4108

Country of Publication

UNITED STATES

Record 42 from database: MEDLINE
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Title

The effect of porphyrins on cellular redox systems: a study on the dark effect of porphyrins on phagocytes.

Author

Koningsberger JC; Van Asbeck BS; Van Hattum J; Wiegman LJ; Van Berge Henegouwen GP; Marx JJ

Address

Department of Gastroenterology, University Hospital Utrecht, The Netherlands.

Source

Eur J Clin Invest, 1993 Nov, 23:11, 716-23

Abstract

Erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) are characterized by skin morbidity, induced by pro-inflammatory reactive oxygen species generated by the photosensitizing properties of protoporphyrin IX and uroporphyrin I. How these porphyrins exert a toxic effect on the liver in the absence of light is poorly understood. We tested the hypothesis that porphyrins can interference with cellular redox systems, by studying the dark effects of protoporphyrin (PP), haematoporphyrin (HP), deuteroporphyrin (DP) and uroporphyrin (UP) on the cellular redox system of phagocytes, and on enzymatic oxyradical generating systems. Both in phagocytic cells and enzymatic systems, a dose-dependent inhibition of chemiluminescence was observed by all porphyrins added. Catalase and SOD-like activity of porphyrins was excluded by oxygraph and ferricytochrome c reduction. However, ferrocytochrome c oxidation was inhibited by porphyrins indicating ferrireductase-like activity. In a Fenton type reaction between H2O2 and PP, we could demonstrate the generation of .OH, or an electronically excited porphyrin species. No influence on phagocyte chemotaxis, phagocytosis and killing-capacity was observed. We conclude that porphyrins do interfere with (cellular) redox systems and can both inhibit and enhance oxygen free radical generation, dependent on the type of redox reaction. Porphyrins can thus affect cellular metabolism. Since H2O2 and PP both readily dissolve in biological membranes, their interaction in the presence of transition metals may contribute to the toxic dark effects of porphyrins as observed in patients with EPP and PCT.

Language of Publication

English

Unique Identifier

94139816

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MeSH Heading (Major)

Phagocytes|*DE/PH; Porphyrins|*PD

MeSH Heading

Chemiluminescence; Cytochrome c|ME; Darkness; Human; Hydroxyl Radical|ME; Neutrophils|DE/PH; Oxidation-Reduction; Superoxides|ME

Publication Type

JOURNAL ARTICLE

ISSN

0014-2972

Country of Publication

ENGLAND

CAS Registry/EC Number

0 (Porphyrins); 11062-77-4 (Superoxides); 3352-57-6 (Hydroxyl Radical); 9007-43-6 (Cytochrome c)

Record 43 from database: MEDLINE
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Title

Involvement of metallothionein and copper in cell proliferation.

Author

W…ostowski T

Address

Institute of Biology, Warsaw University, Bia…ystok, Poland.

Source

Biometals, 1993 Summer, 6:2, 71-6

Abstract

Metallothionein is a low-molecular weight, cysteine-rich, metal-binding protein which has been implicated in the detoxification of toxic metals (cadmium, mercury), metabolism of zinc and copper, as well as in the scavenging of free radicals. Recent evidence suggests that the protein may also be involved in cell proliferation. Based on the experiments carried out so far, it is assumed that the fundamental role of metallothionein in cell proliferation may be to detoxify and/or transfer copper ions from the cytoplasm to the nucleus at the G1/S phase, which in turn participate in some way in nuclear DNA synthesis.

Language of Publication

English

Unique Identifier

93364161

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MeSH Heading (Major)

Cell Division|*; Copper|*ME; Metallothionein|*ME

MeSH Heading

Amino Acid Sequence; Animal; Cell Cycle; Conserved Sequence; Evolution; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0966-0844

Country of Publication

ENGLAND

CAS Registry/EC Number

7440-50-8 (Copper); 9038-94-2 (Metallothionein)

Record 44 from database: MEDLINE
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Title

Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury.

Author

Guyton KZ; Liu Y; Gorospe M; Xu Q; Holbrook NJ

Address

Section on Gene Expression and Aging, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA.

Source

J Biol Chem, 1996 Feb, 271:8, 4138-42

Abstract

The mitogen-activated protein kinase (MAPK) family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. In this study we investigated the factors controlling MAPK activation by H2O2 and explored the impact of altering the pathways to kinase activation on cell survival following H2O2 exposure. Potent activation (10-20-fold) of extracellular signal-regulated protein kinase (ERK2) occurred within 10 min of H2O2 treatment, whereupon rapid inactivation ensued. H2O2 activated ERK2 in several cell types and also moderately activated (3-5-fold) both c-Jun N-terminal kinase and p38/RK/CSBP. Additionally, H2O2 increased the mRNA expression of MAPK-dependent genes c-jun, c-fos, and MAPK phosphatase-1. Suramin pretreatment completely inhibited H2O2 stimulation of ERK2, highlighting a role for growth factor receptors in this activation. Further, ERK2 activation by H2O2 was blocked by pretreatment with either N-acetyl-cysteine, o-phenanthroline, or mannitol, indicating that metal-catalyzed free radical formation mediates the initiation of signal transduction by H2O2. H2O2-stimulated activation of ERK2 was abolished in PC12 cells by inducible or constitutive expression of the dominant negative Ras-N-17 allele. Interestingly, PC12/Ras-N-17 cells were more sensitive than wild-type PC12 cells to H2O2 toxicity. Moreover, NIH 3T3 cells expressing constitutively active MAPK kinase (MEK, the immediate upstream regulator of ERK) were more resistant to H2O2 toxicity, while those expressing kinase-defective MEK were more sensitive, than cells expressing wild-type MEK. Taken together, these studies provide insight into mechanisms of MAPK regulation by H2O2 and suggest that ERK plays a critical role in cell survival following oxidant injury.

Language of Publication

English

Unique Identifier

96223985

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MeSH Heading (Major)

Ca(2+)-Calmodulin Dependent Protein Kinase|*ME; Cell Survival|*DE; Hydrogen Peroxide|*PD; Muscle, Smooth, Vascular|CY/*DE/PH

MeSH Heading

Animal; Aorta|CY/DE/PH; Blotting, Western; Cells, Cultured; Enzyme Activation; Free Radicals|AN/ME; Gene Expression|DE; Genes, fos; Genes, jun; Hela Cells; Human; Kinetics; Luciferase|AN/BI; Mice; Phosphoproteins|IP/ME; Phosphotyrosine|AN; PC12 Cells; Rats; Recombinant Proteins|AN/BI; Transfection; 3T3 Cells

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

Record 45 from database: MEDLINE
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Title

Aluminum salts stimulate luminol-enhanced chemiluminescence production by human neutrophils.

Author

Stankovic A; Mitrovic DR

Address

INSERM U. 18, Lariboisiere Hospital, Paris, France.

Source

Free Radic Res Commun, 1991, 14:1, 47-55

Abstract

Aluminum intoxication is currently thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations seen during long-term hemodialysis and aging. The hypothesis that aluminum toxicity is mediated via an increased free radical production was tested by studying the effects of two aluminum and five other metallic compounds on the production of luminol-enhanced chemiluminescence (LECL) by human neutrophils. AlCl3, Al2(SO4)3 and FeCl3 were found to stimulate LECL production by human neutrophils whereas FeCl2, CuCl, CuCl2, AuCl3 were inactive. Metal chelators such as Desferal, EDTA and DETAPA suppressed aluminum-induced stimulation and depressed cell-dependent LECL below basal levels. Sodium azide and Cytochalasin B greatly depressed both basal and aluminum-induced stimulation of LECL production, suggesting that, in this system, most of this stimulation was due to myeloperoxidase. These results suggest that high tissue aluminum concentrations may induce cell-tissue lesions by stimulating local production or release of mediators of tissue damage.

Language of Publication

English

Unique Identifier

91216480

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MeSH Heading (Major)

Alum Compounds|*PD; Aluminum|*PD; Chlorides|*PD; Luminescence|*; Luminol|*PD; Neutrophils|DE/*PH

MeSH Heading

Azides|PD; Cytochalasin B|PD; Deferoxamine|PD; DTPA|PD; Edetic Acid|PD; Ferric Compounds|PD; Human

Publication Type

JOURNAL ARTICLE

ISSN

8755-0199

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Alum Compounds); 0 (Azides); 0 (Chlorides); 0 (Ferric Compounds); 10043-01-3 (aluminum sulfate); 14930-96-2 (Cytochalasin B); 26628-22-8 (sodium azide); 521-31-3 (Luminol); 60-00-4 (Edetic Acid); 67-43-6 (DTPA); 70-51-9 (Deferoxamine); 7429-90-5 (Aluminum); 7705-08-0 (ferric chloride); 7784-13-6 (aluminum chloride hexahydrate)

Record 46 from database: MEDLINE
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Title

Assay for erythrocyte superoxide dismutase activity in patients with lung cancer and effects on pollution and smoke trace elements.

Author

Martin Mateo MC; Molpeceres LM; Ramos G

Address

Department of Biochemistry, Molecular Biology & Physiology, Faculty of Science, Paseo del Prado de la Magdalena s/n, Valladolid, Spain.

Source

Biol Trace Elem Res, 1997 Dec, 60:3, 215-26

Abstract

The antioxidative effect of CuZnSOD, which catalyzes the dismutation of superoxide anion (O2-), provides a defense against the oxygen toxicity. The object of the study is to evaluate the erythrocytes superoxide dismutase (SOD) activity in two groups of persons (Group I, healthy blood donors; Group II, lung cancer patients), using the spectrophotometric assay of NADH oxidation and the indirect method. The effect of trace elements, such as Al3-, Cr3+, Fe3+, Hg2+, NI2+, and Pb2+ (producing free radicals oxygen and present in pollution and smoke) is also evaluated. The results show the decrease of SOD activity in lung cancer patients with respect to healthy individuals. Likewise, in those patients the enzymatic activity is bigger in early stage (I,II) with respect to advanced one (III) (p < 0.05). The lesser activity when the samples are incubated with Ni or Pb point out that these metals play a role in neoplasm development. In short, the oxidant-antioxidant balance is altered in lung cancer patients.

Language of Publication

English

Unique Identifier

98153078

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MeSH Heading (Major)

Environmental Pollutants|*AE/AN; Erythrocytes|DE/*EN; Lung Neoplasms|BL/*EN/ET; Superoxide Dismutase|*BL; Tobacco Smoke Pollution|*AE/AN; Trace Elements|*AE/AN

MeSH Heading

Adenocarcinoma|BL/EN/ET; Aged; Carcinoma, Large Cell|BL/EN/ET; Carcinoma, Non-Small-Cell Lung|BL/EN/ET; Carcinoma, Small Cell|BL/EN/ET; Carcinoma, Squamous Cell|BL/EN/ET; Comparative Study; Female; Free Radicals; Human; Male; Middle Age; Neoplasm Staging; NAD|CH; Oxidation-Reduction; Spectrophotometry, Ultraviolet

Publication Type

JOURNAL ARTICLE

ISSN

0163-4984

Country of Publication

UNITED STATES

Record 47 from database: MEDLINE
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Title

The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I) [see comments]

Author

Multhaup G; Schlicksupp A; Hesse L; Beher D; Ruppert T; Masters CL; Beyreuther K

Address

ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany.

Source

Science, 1996 Mar, 271:5254, 1406-9

Abstract

The transition metal ion copper(II) has a critical role in chronic neurologic diseases. The amyloid precursor protein (APP) of Alzheimer's disease or a synthetic peptide representing its copper-binding site reduced bound copper(II) to copper(I). This copper ion-mediated redox reaction led to disulfide bond formation in APP, which indicated that free sulfhydryl groups of APP were involved. Neither superoxide nor hydrogen peroxide had an effect on the kinetics of copper(II) reduction. The reduction of copper(II) to copper(I) by APP involves an electron-transfer reaction and could enhance the production of hydroxyl radicals, which could then attack nearby sites. Thus, copper-mediated toxicity may contribute to neurodegeneration in Alzheimer's disease.

Language of Publication

English

Unique Identifier

96173947

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MeSH Heading (Major)

Alzheimer Disease|*ME; Amyloid beta-Protein Precursor|AI/CH/*ME; Copper|*ME

MeSH Heading

Binding Sites; Cysteine|CH; Cystine|ME; Electron Transport; Ferric Compounds|ME; Histidine|CH; Human; Hydrogen Peroxide|ME; Hydroxyl Radical|ME; Oligopeptides|PD; Oxidation-Reduction; Peptide Fragments|CH/ME; Recombinant Fusion Proteins|ME; Spectrum Analysis, Mass; Superoxides|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0036-8075

Country of Publication

UNITED STATES

Record 48 from database: MEDLINE
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Title

Mitochondrial function is involved in LDL oxidation mediated by human cultured endothelial cells.

Author

Mabile L; Meilhac O; Escargueil Blanc I; Troly M; Pieraggi MT; Salvayre R; Nègre Salvayre A

Address

Biochemistry Laboratory (INSERM CJF-9206), Institut Louis Bugnard, CHU Rangueil, Toulouse, France.

Source

Arterioscler Thromb Vasc Biol, 1997 Aug, 17:8, 1575-82

Abstract

Human endothelial cells (ECs) grown under standard conditions are able to generate a basal level of oxygen free radicals and induce progressive oxidation of LDLs. Inhibition of cell-mediated LDL oxidation by superoxide dismutase, EDTA, or desferrioxamine implicates a role for superoxide anion and/or transition metals in this process. The potential role of the mitochondrion was investigated by inducing mitochondrial deenergization by selective photosensitization or the addition of inhibitors of the mitochondrial respiratory chain. Mitochondria of human cultured ECs were selectively damaged by photosensitization of cells labeled with the mitochondrion-selective fluorescent dye 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide under conditions that induced only low levels of toxicity during the time of the experiment. Photosensitized ECs exhibited severe mitochondrial dysfunction, as suggested by the defect in mitochondrial uptake of the mitochondrion-selective fluorescent dyes [rhodamine 123 and 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide] and morphological alterations as shown by transmission electron microscopy. In mitochondria-photosensitized cells, superoxide anion generation was strongly decreased, as was LDL oxidation and the subsequent cytotoxicity. When ECs were incubated with the mitochondrial respiratory-chain inhibitors antimycin A or rotenone or with the carbonylcyanide-m-chlorophenylhydrazone uncoupler rhodamine 123, uptake and subcellular distribution were altered, and concomitantly superoxide anion production and LDL oxidation were strongly decreased. In conclusion, these data suggest that mitochondrial function is required, directly or indirectly, for the production of superoxide anion and the subsequent LDL oxidation by human vascular ECs.

Language of Publication

English

Unique Identifier

97447187

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MeSH Heading (Major)

Endothelium|*CY/*ME; Lipoproteins, LDL Cholesterol|*ME; Mitochondria|*PH/RE

MeSH Heading

omega-N-Methylarginine|PD; Carbonyl Cyanide m-Chlorophenyl Hydrazone|PD; Cell Line; Deferoxamine|PD; Enzyme Inhibitors|PD; Fluorescent Dyes|PD; Human; Ionophores|PD; Light; Mannitol|PD; NG-Nitroarginine Methyl Ester|PD; Oxidation-Reduction; Superoxide Dismutase|AI; Superoxides|ME; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

1079-5642

Country of Publication

UNITED STATES

Record 49 from database: MEDLINE
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Title

Potential carcinogenicity of foundry fumes: a comparative in vivo-in vitro study.

Author

Humfrey CD; Levy LS; Faux SP

Address

Medical Research Council, Institute for Environment and Health, University of Leicester, UK.

Source

Food Chem Toxicol, 1996 Nov, 34:11-12, 1103-11

Abstract

Epidemiological studies of workers exposed to fumes in the iron and steel foundry industry have consistently demonstrated an increased relative risk of lung cancer of approximately 1.4. Foundry fume is a complex mixture of gases and fine particles generated during the casting process when molten metal is poured into sand moulds bound together with organic binders. The chemical composition of fume varies according to foundry process and, specifically, binder composition. Previous in vitro studies have demonstrated that some fumes have mutagenic activity and that this varies with fume type. The current study has examined the potential carcinogenicity of three fumes in a 2-yr in vivo rodent bioassay using an intrabronchial pellet implantation technique. The toxicity and genotoxicity of the fumes were tested concurrently in a number of in vitro assays including those identifying mutagenicity, unscheduled DNA synthesis, free radical DNA damage and micronucleus induction. The rodent bioassay failed to demonstrate a carcinogenic response, although an increase in preneoplastic lesions was seen in all fume-treated groups relative to controls. When tested in vitro, the fumes were positive in many assays and activity correlated with the polycyclic aromatic hydrocarbon content of the fumes. The employment of a combination of in vitro assays for different genotoxic endpoints, such as those presented in the current study, provides information useful for the overall assessment of carcinogenicity of complex mixtures such as foundry fume.

Language of Publication

English

Unique Identifier

97240232

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MeSH Heading (Major)

Bronchi|*DE/PA; Carcinogens|*TO; DNA|BI/*DE; Hazardous Substances|*TO; Metallurgy|*; Polycyclic Hydrocarbons, Aromatic|AN/*TO; Trachea|*DE/PA

MeSH Heading

Animal; Cell Line; Cells, Cultured; Comparative Study; Female; Human; Liver|CY/DE; Lung Neoplasms|CI/EP; Male; Micronuclei|DE; Mutagenicity Tests; Mutagens|TO; Occupational Exposure; Rabbits; Rats; Rats, Wistar; Steel; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0278-6915

Country of Publication

ENGLAND

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