Evidence for superoxide-dependent reduction of Fe3+ and its role in enzyme-generated hydroxyl radical formation

Fong, Kuo-Lan; McCay, Paul B.; Poyer, J. Lee; Misra, Hara P.; Keele, Bernard B.

doi:10.1016/0009-2797(76)90130-7

Cited by 199 publications

(60 citation statements)

References 22 publications

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“…Since the reversal of the effect of xanthine oxidase at pH 6.6 requires, in addition to d-mannitol, the presence of SOD, both '02 and 'OH are evidently involved in causing the vasodilation at this pH. It is also possible that '02, by reducing the catalytic iron involved in the Haber-Weiss reaction, might accelerate the formation of the -OH (32). It would appear that the free radicals, by causing lipid peroxidation, may induce endothelial cell relaxation resulting in vasodilation.…”

Section: Discussionmentioning

confidence: 99%

Free radicals-induced changes in mesenteric microvascular dimensions in the anesthetized cat.

et al. 1983

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Abstract-Effect of free radicals on microvascular dimensions was studied in anes thetized cat intestinal mesentery. Generation of free radicals by xanthine oxidase, acting on endogenous substrates (e.g., xanthine, hypoxanthine), produced sustained vasodilation at pH 7.4 or at pH 6.6. These effects were reversed by superoxide dismutase (SOD), a superoxide radical ('02-) scavenger, at pH 7.4, and by SOD plus hydroxyl radical ('OH) scavenger d-mannitol at pH 6.6. These findings suggest that the sustained vasodilation is caused by '02 and by 'OH derived from '02_ at low pH.

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Section: Discussionmentioning

confidence: 99%

Free radicals-induced changes in mesenteric microvascular dimensions in the anesthetized cat.

et al. 1983

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“…They are ascribed specific functions as supporters of membrane-bound enzymes [l]. This type of lipid is oxidized in the presence of reduced iron or by free radical-producing agents and the subsequent chain reaction is associated with concomitant lipid peroxidation [2]. The reaction is well characterized in subcellular fractions [3] and combinations of subcellular fractions [2].…”

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confidence: 99%

“…This type of lipid is oxidized in the presence of reduced iron or by free radical-producing agents and the subsequent chain reaction is associated with concomitant lipid peroxidation [2]. The reaction is well characterized in subcellular fractions [3] and combinations of subcellular fractions [2]. The loss of lipid [4] as well as protein [5] material from the microsomal membrane has been reported.…”

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confidence: 99%

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The Consequences of Lipid Peroxidation in Isolated Hepatocytes

Högberg

Moldéus

Orrenius

et al. 1975

European Journal of Biochemistry

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Lipid peroxidation was initiated by the addition of either ADP-complexed Fe3 + or cumene hydroperoxide to isolated rat hepatocytes and the resultant biochemical and morphological alterations investigated. As previously observed with microsomes, malonaldehyde formation was associated with the inactivation of glucose-6-phosphatase. Inhibition of microsomal oxidative drug metabolism was correlated with the release and subsequent inactivation of NADPH-cytochrome c reductase, whereas cytochrome P-450 destruction occurred only in the presence of high concentrations of the organic hydroperoxide which were associated with extensive malonaldehyde formation. Under these conditions there were also marked ultrastructural alterations in the hepatocytes which were not apparent after incubation in the presence ofiron (I 187pM Fe3+). The latter treatment was, however, associated with moderate biochemical effects such as glucose-6-phosphatase inactivation and increased membrane permeability. The cellular defence system against lipid peroxidation is discussed and it is concluded that the isolated liver cell system provides a valuable tool for the study of lipid peroxidation and its pathological implications. Because of its widespread toxic effects lipid peroxidation might have pathological implications as has been proposed in connection with iron toxicity [6] and CCI, toxicity [7]. However, the role of lipid peroxidation during the early stages of cell damage leading to cell necrosis has yet to be established.Isolated liver cells produce malonaldehyde, a metabolite of lipid peroxides, upon exposer to ADP-complexed iron or the organic peroxide cumene hydroEn:ymc.s. Collagenase (EC 3.4.24.3); Hyaluronidase or hyaluronate 4-glycanohydrolase (EC 3.2.1.35); NADPH-cytcchrome c reductase (EC 1.6.2.4); Glucose 6-phosphatase (EC 3.1.3.9).peroxide [8]. Malonaldehyde production, which is readily monitored in this isolated-cell system, is probably catalyzed by the drug-hydroxylating enzyme system located in the endoplasmic reticulum and is thus comparable with the enzyme-dependent lipid peroxidation reactions of isolated microsomes [9,10]. The isolated cell system, however, differs from a microsomal system in being fortified with natural inhibitors, which alter the response to agents that stimulate lipid peroxidation [8,11]. The purpose of this work was to characterize some early alterations in isolated hepatocytes in which malonaldehyde production had been induced. MATERIALS AND METHODSThe cell preparation and incubation techniques were the same as described previously [8,11]. Lipid peroxide formation was initiated by addition of ADPcomplexediron(stocksolution50mMADP + 1.87mM FeC1,) or an aqueous solution of cumene hydroperoxide (stock solution 30 mM). The reaction was followed by the withdrawal of aliquots (0.2 ml) of the whole incubation mixture for spectrophotometric measurements of thiobarbituric-acid-reacting substances at 535 nm (malonaldehyde) [12].

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“…(1) catalyst Traces of free iron salts are present intra-cellularly [8,9] and in some extracellular fluids [10], whilst O~-and H202 can be produced by the action of several enzymes and by activated phagocytes as well as by the autoxidation of compounds such as thiols [2]. Exposure of physiological concentrations of reduced glutathione, GSH, to Fe(II) salts gives rise to hydroxyl radicals in a O~--and H202-dependent reaction [11] and have suggested that this reaction is a significant source of OH" radicals in vivo.…”

Section: Introductionmentioning

confidence: 99%

Superoxide‐dependent formation of hydroxyl radicals from NADH and NADPH in the presence of iron salts

Rowley

Halliwell

1982

FEBS Letters

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Evidence for superoxide-dependent reduction of Fe3+ and its role in enzyme-generated hydroxyl radical formation

Cited by 199 publications

References 22 publications

Free radicals-induced changes in mesenteric microvascular dimensions in the anesthetized cat.

Free radicals-induced changes in mesenteric microvascular dimensions in the anesthetized cat.

The Consequences of Lipid Peroxidation in Isolated Hepatocytes

Superoxide‐dependent formation of hydroxyl radicals from NADH and NADPH in the presence of iron salts

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