Journal ArticleDOI
Role of hydroxyl radicals in the iron-ethylenediaminetetraacetic acid mediated stimulation of microsomal oxidation of ethanol.
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During microsomal electron transfer, conditions may be appropriate for a Fenton type or a modified Haber-Weiss type of reaction to occur, leading to the production of hydroxyl radicals.Abstract:
The microsomal oxidation of ethanol or 1-butanol was increased by ferrous ammonium sulfate-ethylenediaminetetraacetic acid (1:2) (Fe-EDTA) (3.4-50 microM). The increase was blocked by hydroxyl radical scavenging agents such as dimethyl sulfoxide or mannitol. The activities of aminopyrine demethylase or aniline hydroxylase were not affected by Fe-EDTA. The accumulation of H2O2 was decreased in the presence of Fe-EDTA, consistent with an increased utilization of H2O2. Other investigators have shown that Fe-EDTA increases the formation of hydroxyl radicals in systems where superoxide radicals are generated. The stimulation by Fe-EDTA appears to represent a pathway involving hydroxyl radicals rather than catalase because (1) stimulation occurred in the presence of azide, which inhibits catalase, (2) stimulation occurred in the presence of 1-butanol, which is not an effective substrate for catalase, and (3) stimulation was blocked by hydroxyl radical scavenging agents, which do not affect catalase-mediated oxidation of ethanol. A possible role for contaminating iron in the H2O or buffers could be ruled out since similar results were obtained with or without chelex-100 treatment of these solutions. The stimulatory effect by Fe-EDTA required microsomal electron transfer with NADPH, and H2O2 could not replace the NADPH-generating system. In the absence of microsomes or catalase, Fe-EDTA also stimulated the coupled oxidation of ethanol during the oxidation of xanthine by xanthine oxidase. These results suggest that during microsomal electrom transfer, conditions may be appropriate for a Fenton type or a modified Haber-Weiss type of reaction to occur, leading to the production of hydroxyl radicals.read more
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Production of formaldehyde during metabolism of dimethyl sulfoxide by hydroxyl radical-generating systems
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Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride— and iron-dependent microsomal lipid peroxidation
Tirso Castillo,Dennis R. Koop,Seiichiro Kamimura,George Triadafilopoulos,Hidekazu Tsukamoto,Hidekazu Tsukamoto +5 more
TL;DR: Induction of P‐450 2E1 at an advanced stage of experimental ALD demonstrates a major role of this cytochrome in the enhanced basal lipid peroxidation of microsomes obtained from livers with ALD and a major contribution to the increased vulnerability of these microsome to ferric citrate and carbon tetrachloride—induced per oxidation.
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The toxicology of molecular oxygen.
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The role of iron chelates in hydroxyl radical production by rat liver microsomes, NADPH-cytochrome P-450 reductase and xanthine oxidase☆
TL;DR: The results indicate that the ability of iron to promote hydroxyl radical production and the role that superoxide plays as a reductant of iron depends on the nature of the system as well as the chelating agent employed.
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Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors.
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