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 ra dical formation and lipid peroxidation was analyzed. Ethanol induces a dose-dependent increase in lipid peroxidation in brain homogenates. T he peroxidative effects of alcohol seem to be related to both cytochro me P450 and the ethanol-inducible form of cytochrome P450 (CYP2E1), be cause preincubation with metyrapone (an inhibitor of cytochrome P450) or with an antibody against CYP2E1 abolished the ethanol-increased lip id peroxidation. Using the formation of dichlorofluorescein, we also d emonstrated that both in vitro and chronic alcohol exposure significan tly enhanced the formation of oxygen radical species in synaptosomes. Chronic alcohol treatment also leads to an induction of cytochrome P45 0 (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 t he levels of superoxide dismutase and catalase activities. This mechan ism could be involved in the toxic effects of ethanol on brain and mem brane alterations occurring after chronic ethanol intake.