100 Scientific Studies -- Free Radicals

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Table Of Contents

100 Studies of Free Radicals:

The Cause Of Virtually All Disease

Go To The Home Page For Free Radical Information

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Number	Title	Comments
...1...	Oxidative mechanisms in the toxicity of metal ions.
...2...	Nutrition and metal toxicity.
...3...	Role of Fenton chemistry in thiol-induced toxicity and apoptosis.
...4...	The protective role of ceruloplasmin against the activity of free radicals in brain ischaemia.
...5...	A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals.
...6...	Biochemical aspects of free radicals.	The chain-breaking antioxidant status can clearly be influenced by the dietary content of substances such as vitamins E and C.
...7...	Variability in response to D-penicillamine: pharmacokinetic insights.
...8...	Oxidants and human disease: some new concepts.
...9...	Transition metals as catalysts of "autoxidation" reactions.
...10...	Surface reactivity in the pathogenic response to particulates.
...11...	Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals.
...12...	Free radical generation by selenium compounds and their prooxidant toxicity.
...13...	Oxygen toxicity: an introduction.
...14...	Oxygen toxicity: an introduction.
...15...	Use of iron chelators in preventing hydroxyl radical damage: adult respiratory distress syndrome as an experimental model for the pathophysiology and treatment of oxygen-radical-mediated tissue damage.
...16...	Oxygen free radicals in nephrology.
...17...	Reactive oxygen species and Alzheimer's disease.
...18...	Therapeutic iron chelators and their potential side-effects.
...19...	Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences [published erratum appears in Free Radic Biol Med 1991;10(3-4):249]
...20...	Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity.
Menu Position 20
...21...	Free radicals in toxicology.
...22...	Free radicals and environmental toxins.
...23...	Free radicals derived from oxygen, and medicine.
...24...	Liver copper storage and transport during development: implications for cytotoxicity.
...25...	Radiation and aging: free radical damage, biological response and possible antioxidant intervention.
...26...	Role of oxygen free radicals in carcinogenesis and brain ischemia.
...27...	Protein glycation and oxidative stress in diabetes mellitus and ageing.
...28...	Active oxygen in neuromuscular disorders.
...29...	The role of iron in oxygen-mediated toxicities.
...30...	Oxidative stress: a role in the pathogenesis of Parkinson's disease.
...31...	Bleomycin pharmacology: mechanism of action and resistance, and clinical pharmacokinetics.
...32...	Ferritin and ceruloplasmin in oxidative damage: review and recent findings.
...33...	Ferritin as a source of iron for oxidative damage [see comments]
...34...	Involvement of metallothionein and copper in cell proliferation.
...35...	Emergent issues in the genetics of intestinal neoplasia.
...36...	Role of oxygen in phagocyte microbicidal action.
...37...	Pharmacogenetics in biological perspective.
...38...	Multiple identity enactments and multiple personality disorder: a sociocognitive perspective [see comments]
...39...	Modulation of mitogenesis by liver fatty acid binding protein.
...40...	The rise and fall in information-processing rates over the life span.
Menu Position 40
...41...	Molecular and genetic epidemiology of hepatocellular carcinoma: studies in China and Senegal.
...42...	The inflammatory response and tissue damage. The example of renal scars following acute renal infection.
...43...	Pituitary-thyroid relationships in hypothyroidism.
..44...	Regulation of new fat cell formation.
...45...	Future prospects in antiviral therapy.
...46...	The traditional toxicologic paradigm is correct: dose influences mechanism.
...47...	Role played by vasopressin (and of an adrenalpostpituitary imbalance) in the development of cancerous diseases.
...48...	Prognostic factors in nasopharyngeal carcinoma investigated by computer tomography--an analysis of 659 patients [see comments]
...49...	A reviewer's perspective on multiple endpoint issues in clinical trials.
...50...	Analyzing the functional consequences of transmitter complexity.
...51...	Constrictive and restrictive pulmonary hypertension in the newborn and infant.
...52...	The nature of the mineral component of bone and the mechanism of calcification.
...53...	Molecular biology of serotonin (5-HT) receptors.
...54...	On cancer risk estimation of urban air pollution.
...55...	The control of hematopoiesis and leukemia: from basic biology to the clinic.
...56...	Physiopathology of primary periodontitis associated with plaque. Microbial and host factors. A review. Part 1.
...57...	Multiple serotonin receptor subtypes: molecular cloning and functional expression.
...58...	Turning point in the design of linkage studies of schizophrenia.
...59...	Analysis of the molecular basis of neuropathogenesis of RNA viruses in experimental animals: relevance for human disease?
...60...	Antiviral drugs: present status and future prospects.
Menu Position 60
...61...	Culpability and pain management/control in peripheral vascular disease using the ethics of principles and care.
...62...	Biologic synergism and parallelism.
...63...	A multifactorial approach to the study of gender characteristics.
...64...	Cell types involved in replication and distribution of human cytomegalovirus.
...65...	Interaction between human carcinogens.
...66...	Risk ratios and risk differences in estimating the effect of risk factors for cardiovascular disease in the elderly.
...67...	Genetics of coeliac disease.
...68...	Perspectives in antiviral chemotherapy.
...69...	Approaches to interferon combination therapy in the treatment of AIDS.
...70...	Adherence & colonization properties of Vibrio cholerae & diarrhoeagenic Escherichia coli.
...71...	Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics.
...72...	The thyrotropin receptor.
...73...	Nontraditional epidemiologic approaches in the analysis of gene-environment interaction: case-control studies with no controls!
...74...	Molecular aspects of insulin-like growth factors, their binding proteins and receptors.
...75...	Platelet-derived growth factor: a multifunctional regulator of normal and abnormal cell growth.
...76...	Biology and molecular biology of epidermal cell-derived thymocyte activating factor.
...77...	Should we expand the TORCH complex? A description of clinical and diagnostic aspects of selected old and new agents.
...78...	Treatment of persistent active herpesvirus infections.
...79...	Thromboxane A2 and leukotrienes are eicosanoid mediators of shock and ischemic disorders.
...80...	PDGF-like growth factors in autocrine stimulation of growth.
Menu Position 80
...81...	The heart in hypertension: unresolved conceptual challenges. Special lecture.
...82...	Function of dietary polyunsaturated fatty acids in the nervous system.
...83...	The complexity of dopamine receptors and psychopharmacotherapy in children.
...84...	Mx proteins: GTPases involved in the interferon-induced antiviral state.
...85...	T cell adhesion, avidity regulation and signaling: a molecular analysis of CD2.
...86...	The GABAA receptor channel mediated chloride ion translocation through the plasma membrane: new insights from 36Cl- ion flux measurements.
...87...	The influence of chemical structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 55 different human carcinogen exposures.
...88...	GABA receptor molecules of insects.
...89...	Non-P-glycoprotein multidrug resistance in cell lines which are defective in the cellular accumulation of drug.
...90...	The autonomic nervous system and adrenergic receptors in pediatric practice.
...91...	Arrhythmia control by prolonging repolarization: the concept and its potential therapeutic impact.
...92...	Biochemical markers of aging.
...93...	Modulation of arachidonic acid metabolites as potential therapy of asthma.
...94...	Pharmacological mechanisms of opioid analgesics.
...95...	The molecular control of hemopoiesis and leukemia.
...96...	DNA lesions, inducible DNA repair, and cell division: three key factors in mutagenesis and carcinogenesis.
...97...	Development of breast cancer chemopreventive drugs.
...98...	The multiplicity of actions of benzodiazepine receptor ligands.
...99...	Inhibitors of enkephalin-degrading enzymes as potential therapeutic agents.
...100...	A hypothesis on the primate neocortex evolution: column-multiplication hypothesis.

HealthGate Documents

Record 1 from database: MEDLINE
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Title: Oxidative mechanisms in the toxicity of metal ions.
Author: Stohs SJ; Bagchi D
Address: School of Pharmacy, Creighton University, Omaha, NE 68178, USA.
Source: Free Radic Biol Med, 1995 Feb, 18:2, 321-36
Abstract: The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.
Language of Publication: English
Unique Identifier: 95262971

MeSH Heading (Major): Metals|*TO; Oxidative Stress|*
MeSH Heading: Animal; Human; Oxidation-Reduction; Reactive Oxygen Species|ME; Support, U.S. Gov't, Non-P.H.S.

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0891-5849
Country of Publication: UNITED STATES

Record 2 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

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 3 from database: MEDLINE
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Title: Role of Fenton chemistry in thiol-induced toxicity and apoptosis.
Author: Held KD; Sylvester FC; Hopcia KL; Biaglow JE
Address: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, USA.
Source: Radiat Res, 1996 May, 145:5, 542-53
Abstract: Under certain conditions, many radioprotective thiols can be toxic, causing loss of colony-forming ability in cultured mammalian cells in a biphasic fashion whereby the thiols are not toxic at high or low concentrations of the drug, but cause decreased clonogenicity at intermediate (0.2-1.0 mM) drug levels. This symposium paper summarizes our studies using dithiothreitol (DTT) as a model thiol to demonstrate the role of Fenton chemistry in thiol toxicity. The toxicity of DTT in V79 cells has several characteristics: it is dependent on the medium used during exposure of cells to the drug; the toxicity is decreased or prevented by addition of catalase exogenously, but superoxide dismutase has no effect; the toxicity is increased by addition of copper, either free or derived from ceruloplasmin in serum; and the toxicity can be modified intracellularly by altering glucose availability or pentose cycle activity. Thus the data are consistent with a mechanism whereby DTT oxidation produces H2O2 in a reaction catalyzed by metals, predominantly copper, followed by reaction of H2O2 in a metal-catalyzed Fenton reaction to produce the ultimate toxic species, .OH. Studies comparing 12 thiols have shown that the magnitude of cell killing and pattern of dependence on thiol concentration vary among the different agents, with the toxicity depending on the interplay between the rates of two reactions: thiol oxidation and the reaction between the thiol and the H2O2 produced during the thiol oxidation. The addition of other metals, e.g. Zn2+, and metal chelators, e.g. EDTA, can also alter DTT toxicity by altering the rates of thiol oxidation or the Fenton reaction. Recent studies have shown that in certain cell lines thiols can also cause apoptosis in a biphasic pattern, with little apoptosis at low or high drug concentrations but greatly increased apoptosis levels at intermediate (approximately 3 mM) thiol concentrations. There appears to be a good correlation between those thiols that cause loss of clonogenicity and those that induce apoptosis, suggesting similar mechanisms may be involved in both end points. However, thiol-induced apoptosis is not prevented by addition of exogenous catalase. These observations are discussed in relation to the possible role of Fenton chemistry in induction of apoptosis by thiols.
Language of Publication: English
Unique Identifier: 96198949

MeSH Heading (Major): Apoptosis|*DE; Cell Survival|*DE; Hydrogen Peroxide|*; Iron|*; Sulfhydryl Compounds|*PD/TO
MeSH Heading: Animal; Cell Line; Chelating Agents|PD; Dithiothreitol|PD/TO; Human; Hydroxyl Radical; Metals|PD; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0033-7587
Country of Publication: UNITED STATES

Record 4 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

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 5 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

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 6 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

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 7 from database: MEDLINE
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Title: Variability in response to D-penicillamine: pharmacokinetic insights.
Author: Joyce DA
Address: Department of Clinical Pharmacology, Queen Elizabeth II Medical Centre, University of Western Australia, Nedlands.
Source: Agents Actions Suppl, 1993, 44:, 203-7
Abstract: D-Penicillamine (D-Pen) is one of a group of chemically similar drugs which are efficacious in rheumatoid arthritis and which have similar patterns of biotransformation and similar toxicity. These similarities suggest associations between the transformations of D-Pen and it's toxicity and efficacy. Oxidation, methylation, formation of stable adducts with protein, interaction with metals and reduction of oxygen species have been shown in-vivo or in-vitro. Metabolism to a sulphoxide may occur and may be relevant to toxicity. Intracellular concentrations of D-Pen and metabolites are largely unknown.
Language of Publication: English
Unique Identifier: 93383755

MeSH Heading (Major): Penicillamine|AE/*PK
MeSH Heading: Biotransformation|PH; Comparative Study; Disulfides|ME; Free Radicals; Human; Metals|ME; Methylation; Oxygen|ME; Sulfoxides|ME; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0379-0363
Country of Publication: SWITZERLAND
CAS Registry/EC Number: 0 (Disulfides); 0 (Free Radicals); 0 (Metals); 0 (Sulfoxides); 52-67-5 (Penicillamine); 7782-44-7 (Oxygen)

Record 8 from database: MEDLINE
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Title: Oxidants and human disease: some new concepts.
Author: Halliwell B
Address: Department of Biochemistry, University of London King's College, UK.
Source: FASEB J, 1987 Nov, 1:5, 358-64
Abstract: Oxidant species such as superoxide radical (O.2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.), and lipid peroxides (LOOH) are becoming increasingly implicated in human disease. However, the question of whether such oxidants are a major cause of tissue injury in human disease or are merely produced during such injury has been difficult to answer because of inadequate experimental techniques, and possibly because of an overemphasis on lipid peroxidation as a mechanism of oxidant injury. Recent developments in methodology, in our understanding of the primary mechanism of oxidant toxicity to cells, and in concepts of antioxidant protection are reviewed. Good evidence now exists for some role of oxidant damage to tissues in the pathology of several human diseases, including rheumatoid arthritis, reperfusion injury, immune injury to lung and kidney, and cerebral trauma or ischemia. These have led to promising suggestions for new therapeutic approaches.
Language of Publication: English
Unique Identifier: 88056036

MeSH Heading (Major): Disease|*ET/ME; Oxygen|*ME
MeSH Heading: Antioxidants|TU; DNA|ME; Free Radicals; Human; Hydrogen Peroxide|AE/ME; Hydroxides|AE/ME; Ions; Lipid Peroxides|AE/ME; Metals|PD; Superoxides|AE/ME

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0892-6638
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Antioxidants); 0 (Free Radicals); 0 (Hydroxides); 0 (Ions); 0 (Lipid Peroxides); 0 (Metals); 11062-77-4 (Superoxides); 3352-57-6 (Hydroxyl Radical); 7722-84-1 (Hydrogen Peroxide); 7782-44-7 (Oxygen); 9007-49-2 (DNA)

Record 9 from database: MEDLINE
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Title: Transition metals as catalysts of "autoxidation" reactions.
Author: Miller DM; Buettner GR; Aust SD
Address: Department of Chemistry and Biochemistry, Utah State University, Logan 84322-0300.
Source: Free Radic Biol Med, 1990, 8:1, 95-108
Abstract: Superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (.OH) produced from the "autoxidation" of biomolecules, such as ascorbate, catecholamines, or thiols, have been implicated in numerous toxicities. However, the direct reaction of dioxygen with the vast majority of biomolecules, including those listed above, is spin forbidden, a condition which imposes a severe kinetic limitation on this reaction pathway. Therefore, an alternate mechanism must be invoked to explain the "autoxidations" reactions frequently reported. Transition metals are efficient catalysts of redox reactions and their reactions with dioxygen are not spin restricted. Therefore it is likely that the "autoxidation" observed for many biomolecules is, in fact, metal catalyzed. In this paper we discuss: 1) the quantum mechanic, thermodynamic, and kinetic aspects of the reactions of dioxygen with biomolecules; 2) the involvement of transition metals in biomolecule oxidation; and 3) the biological implications of metal catalyzed oxidations. We hypothesize that true autoxidation of biomolecules does not occur in biological systems, instead the "autoxidation" of biomolecules is the result of transition metals bound by the biomolecules.
Language of Publication: English
Unique Identifier: 90215326

MeSH Heading (Major): Metals|*ME/TO; Oxygen|*ME
MeSH Heading: Animal; Catalysis; Chelating Agents; Copper|ME; Free Radicals; Human; Iron|ME; Models, Chemical; Oxidation-Reduction; Thermodynamics

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0891-5849
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Chelating Agents); 0 (Free Radicals); 0 (Metals); 12185-07-8 (dioxygen); 7439-89-6 (Iron); 7440-50-8 (Copper); 7782-44-7 (Oxygen)

Record 10 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

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 11 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

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 12 from database: MEDLINE
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Title: Free radical generation by selenium compounds and their prooxidant toxicity.
Author: Spallholz JE
Address: Texas Technology University, Lubbock 79404, USA.
Source: Biomed Environ Sci, 1997 Sep, 10:2-3, 260-70
Abstract: Selenium (Se) and many of its compounds are among the most toxic of nutrients. Selenium toxicity was first described in range animals in the western United States in the 1930's which consumed "selenium accumulator" plants of the genus Astragalus, Xylorrhiza, Oonopsis, and Stanleya. Selenites and selenates from the soil accumulate in these plants primarily as methylated selenium compounds and plants evolve dimethyldiselenide and dimethylselenide. Dietary selenium, primarily as selenomethionine and selenocysteine for humans fulfill the dietary requirement for selenoenzymes and proteins. In humans and animals excessive dietary selenium may be toxic. In vitro, selenium compounds such as selenite, selenium dioxide and diselenides react with thiols, such as glutathione, producing superoxide and other reactive oxygen species. This catalytic reaction of selenium compounds with thiols likely accounts for selenium toxicity to cells ex vivo and in vivo where the major glutathione producing organ, the liver, is also the major target organ of selenium toxicity. Selenium enzymes and selenoethers that do not readily form a selenide (RSe-) anion and compounds such as Ebselen where selenium is sequestered, are not toxic. Methylation of selenium by both plants and animals serves to detoxify selenium by generating methylselenides. Alternatively, full reduction of Se to elemental selenium (Se0) as done by some bacteria and the formation of heavy metal selenides such as Ag2Se or Hg2Se, results in a non-catalytic non-toxic form of selenium. This catalytic prooxidant attribute of some selenium compounds appears to account for its toxicity when such activity exceeds plant and animal methylation reactions and antioxidant defenses. This prooxidant activity may also account for cellular apoptosis and may provide a useful pharmaceutical application for selenium compounds as antibacterial, antiviral, antifungal and anticancer agents.
Language of Publication: English
Unique Identifier: 97460952

MeSH Heading (Major): Reactive Oxygen Species|*; Selenium Compounds|*TO
MeSH Heading: Animal; Free Radicals; Human

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0895-3988
Country of Publication: UNITED STATES

Record 13 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

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 14 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

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 15 from database: MEDLINE
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Title: Use of iron chelators in preventing hydroxyl radical damage: adult respiratory distress syndrome as an experimental model for the pathophysiology and treatment of oxygen-radical-mediated tissue damage.
Author: Marx JJ; van Asbeck BS
Address: Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
Source: Acta Haematol, 1996, 95:1, 49-62
Abstract: Tissue damage in many diseases is caused by hydroxyl radicals, generated during single electron reduction of oxygen. The first step is usually the formation of the superoxide radical. This radical is constantly formed in all living cells, and in particular during activation of phagocytes or during reoxygenation following ischaemia. Damage, however, only occurs in the presence of catalytic transition metals of which iron is the most important in human pathology. Oxygen-radical-mediated damage can be prevented by iron chelators, as has been demonstrated in numerous in vitro and in vivo experiments. A description is given as to how toxic oxygen products are formed in biological systems, and how organisms succeed in preventing autodestruction by scavenger molecules. The use of iron chelators to prevent oxygen radical damage is reviewed with emphasis on possible clinical applications. The adult respiratory distress syndrome is described in more detail as a model for oxygen-radical-mediated damage that can be successfully prevented with iron chelators.
Language of Publication: English
Unique Identifier: 96185296

MeSH Heading (Major): Hydroxyl Radical|*AE; Iron Chelating Agents|*TU; Respiratory Distress Syndrome, Adult|ET/*PC
MeSH Heading: Free Radical Scavengers; Free Radicals; Human; Iron|ME; Oxidation-Reduction; Reactive Oxygen Species|ME

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0001-5792
Country of Publication: SWITZERLAND

Record 16 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

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 17 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

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 18 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

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 19 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

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 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

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: 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

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 22 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

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 23 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

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 24 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

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 25 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

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 26 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

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 27 from database: MEDLINE
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Title: Protein glycation and oxidative stress in diabetes mellitus and ageing.
Author: Wolff SP; Jiang ZY; Hunt JV
Address: Department of Clinical Pharmacology, University College London, UK.
Source: Free Radic Biol Med, 1991, 10:5, 339-52
Abstract: Hyperglycemia is increasingly regarded as the cause of the diabetic complications, in particular via the ability of glucose to glycate proteins and generate Maillard browning products which cross-link proteins and render them brown and fluorescent in vitro. Similar changes occur in vivo to long-lived proteins in diabetes mellitus as well as in ageing. The evidence supporting this route of glucose toxicity is discussed in the context of the ability of glucose to oxidize in vitro (catalyzed by trace amounts of transition metal) generating hydrogen peroxide, highly reactive oxidants, and protein-reactive ketoaldehyde compounds. It is suggested that protein browning in vivo may not result from the reactions of glucose with protein but from the transition metal-catalyzed reactions of other small autoxidisable substrates, such as ascorbate, with protein. Overall, studies of glycation and protein browning suggest a critical role for oxidative processes perhaps involving decompartmentalized transition metals and a variety of low molecular weight reducing agents in diabetes mellitus and ageing.
Language of Publication: English
Unique Identifier: 91309904

MeSH Heading (Major): Aging|*; Diabetes Mellitus|ET/*ME/PP; Glucose|*TO; Proteins|*ME
MeSH Heading: Free Radicals; Glycosylation; Human; Support, Non-U.S. Gov't

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
ISSN: 0891-5849
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Free Radicals); 50-99-7 (Glucose)

Record 28 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

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 29 from database: MEDLINE
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Title: The role of iron in oxygen-mediated toxicities.
Author: Ryan TP; Aust SD
Address: Biotechnology Center, Utah State University, Logan 84322-4705.
Source: Crit Rev Toxicol, 1992, 22:2, 119-41
Abstract: The transition metal iron is capable of catalyzing redox reactions between biomolecules and oxygen that would not occur if catalytically active iron were not present. Although these biological oxidations (which are known collectively as "oxidative stress") have been implicated in numerous toxicities, the exact role of the iron catalyst remains to be elucidated. This review focuses on our current understanding of the role of iron in oxidative stress, discussing biologically relevant sources, biochemical forms, and reaction mechanisms of iron as a catalyst of biomolecular oxidations. Specific toxicities in which alterations in normal iron metabolism is thought to overwhelm the body's antioxidant defense system are presented, and future treatment regimens involving novel antioxidant drugs are discussed.
Language of Publication: English
Unique Identifier: 92378771

MeSH Heading (Major): Iron|*ME/TO; Oxygen|*ME
MeSH Heading: Atherosclerosis|ME; Biological Availability; Free Radicals; Human; Neoplasms|ME; Oxidation-Reduction; Reperfusion Injury|ME; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC
ISSN: 1040-8444
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Free Radicals); 7439-89-6 (Iron); 7782-44-7 (Oxygen)

Record 30 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

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 31 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

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 32 from database: MEDLINE
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Title: Ferritin and ceruloplasmin in oxidative damage: review and recent findings.
Author: de Silva DM; Aust SD
Address: Biotechnology Center, Utah State University, Logan 84322-4705.
Source: Can J Physiol Pharmacol, 1993 Sep, 71:9, 715-20
Abstract: The oxidation of biomolecules such as lipid, protein, and DNA is associated with a variety of toxicities and pathologies. In an all-encompassing definition these oxidative processes have been referred to as "oxidative stress." Although the direct reaction between molecular oxygen and most biomolecules is spin forbidden, this reaction can be efficiently catalyzed by transition metals such as iron and copper. Iron especially has been demonstrated to be a potent catalyst of biological oxidations. This review focuses on the relationship between iron and copper with respect to the copper protein ceruloplasmin, which may play a role in iron homeostasis by catalyzing the oxidation of iron as it is placed in ferritin.
Language of Publication: English
Unique Identifier: 94147244

MeSH Heading (Major): Ceruloplasmin|*PH; Ferritin|*PH
MeSH Heading: Animal; Copper|ME; Free Radicals|AE; Human; Iron|ME; Oxidation-Reduction; Support, U.S. Gov't, P.H.S.

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0008-4212
Country of Publication: CANADA
CAS Registry/EC Number: EC 1.16.3.1 (Ceruloplasmin); 0 (Free Radicals); 7439-89-6 (Iron); 7440-50-8 (Copper); 9007-73-2 (Ferritin)

Record 33 from database: MEDLINE
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Title: Ferritin as a source of iron for oxidative damage [see comments]
Author: Reif DW
Address: Biology Department, Fisons Pharmaceuticals, Rochester, NY 14603.
Source: Free Radic Biol Med, 1992, 12:5, 417-27
Abstract: The generation of deleterious activated oxygen species capable of damaging DNA, lipids, and proteins requires a catalyst such as iron. Once released, ferritin iron is capable of catalyzing these reactions. Thus, agents that promote iron release may lead to increased oxidative damage. The superoxide anion formed enzymatically, radiolytically, via metal-catalyzed oxidations, or by redox cycling xenobiotics reductively mobilizes ferritin iron and promotes oxidative damage. In addition, a growing list of compounds capable of undergoing single electron oxidation/reduction reactions exemplified by paraquat, adriamycin, and alloxan have been reported to release iron from ferritin. Because the rapid removal of iron from ferritin requires reduction of the iron core, it is not surprising that the reduction potential of a compound is a primary factor that determines whether a compound will mobilize ferritin iron. The reduction potential does not, however, predict the rate of iron release. Therefore, ferritin-dependent oxidative damage may be involved in the pathogenesis of diseases where increased superoxide formation occurs and the toxicity of chemicals that increase superoxide production or have an adequate reduction potential to mobilize ferritin iron.
Language of Publication: English
Unique Identifier: 92275421

MeSH Heading (Major): Ferritin|*ME; Iron|*ME; Lipid Peroxidation|*; Oxygen|*ME
MeSH Heading: Animal; Human; Nitric Oxide|ME; Oxidation-Reduction; Superoxides|ME; Xenobiotics|ME

Publication Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
ISSN: 0891-5849
Country of Publication: UNITED STATES
CAS Registry/EC Number: 0 (Xenobiotics); 10102-43-9 (Nitric Oxide); 11062-77-4 (Superoxides); 7439-89-6 (Iron); 7782-44-7 (Oxygen); 9007-73-2 (Ferritin)

Record 34 from database: MEDLINE
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