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Ethanol-induced oxidative stress: basic knowledge
Authors:Mario Comporti  Cinzia Signorini  Silvia Leoncini  Concetta Gardi  Lucia Ciccoli  Anna Giardini  Daniela Vecchio  Beatrice Arezzini
Affiliation:Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, via A. Moro, 53100 Siena, Italy
Abstract:After a general introduction, the main pathways of ethanol metabolism (alcohol dehydrogenase, catalase, coupling of catalase with NADPH oxidase and microsomal ethanol-oxidizing system) are shortly reviewed. The cytochrome P450 isoform (CYP2E1) specifically involved in ethanol oxidation is discussed. The acetaldehyde metabolism and the shift of the NAD/NADH ratio in the cellular environment (reductive stress) are stressed. The toxic effects of acetaldehyde are mentioned. The ethanol-induced oxidative stress: the increased MDA formation by incubated liver preparations, the absorption of conjugated dienes in mitochondrial and microsomal lipids and the decrease in the most unsaturated fatty acids in liver cell membranes are discussed. The formation of carbon-centered (1-hydroxyethyl) and oxygen-centered (hydroxyl) radicals during the metabolism of ethanol is considered: the generation of hydroxyethyl radicals, which occurs likely during the process of univalent reduction of dioxygen, is highlighted and is carried out by ferric cytochrome P450 oxy-complex (P450–Fe3+O2·−) formed during the reduction of heme-oxygen. The ethanol-induced lipid peroxidation has been evaluated, and it has been shown that plasma F2-isoprostanes are increased in ethanol toxicity.
Keywords:CYP2E1 isoform   Ethanol metabolism   Hydroxyethyl radicals   Liver-free non-protein bound iron   Oxidative stress   Plasma isoprostanes
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