Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption.
The effect of chronic and in vitro ethanol exposure on brain oxygen radical formation and lipid peroxidation was analyzed. Ethanol induces a dose-dependent increase in lipid peroxidation in brain homogenates. The peroxidative effects of alcohol seem to be related to both cytochrome P450 and the ethanol-inducible form of cytochrome P450 (CYP2E1), because preincubation with metyrapone (an inhibitor of cytochrome P450) or with an antibody against CYP2E1 abolished the ethanol-increased lipid peroxidation. Using the formation of dichlorofluorescein, we also demonstrated that both in vitro and chronic alcohol exposure significantly enhanced the formation of oxygen radical species in synaptosomes. Chronic alcohol treatment also leads to an induction of cytochrome P450 (230%), NADPH cytochrome c reductase (180%), NADPH oxidation (184%), and CYP2E1 in brain microsomes. In addition, this treatment produced a decrease in the GSH/GSSG ratio in brain and significantly enhanced the levels of superoxide dismutase and catalase activities. This mechanism could be involved in the toxic effects of ethanol on brain and membrane alterations occurring after chronic ethanol intake.
Montoliu
C
C
Instituto de Investigaciones Citológicas, Hospital La Fe, Valencia, Spain.
Vallés
S
S
Renau-Piqueras
J
J
Guerri
C
C
D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D019803:Glutathione Disulfide; D015151:Immunoblotting; D007536:Isomerism; D015227:Lipid Peroxidation / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D005609:Free Radicals; D017382:Reactive Oxygen Species; D000431:Ethanol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide