Alcohol-Induced Hepatotoxicity: A Role for Oxygen Free Radicals

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Abstract
Perfusion of isolated rat livers with ethanol at a concentration of 2g/l (%o) resulted in a release of glutamate-pyruvate-transaminase (GPT) and sorbitol dehydrogenase (SDH) into the perfusate as markers of toxicity. Inhibition of alcohol dehydrogenase by 4-methylpyrazole or of aldehyde dehydrogenase by cyanamide totally abolished ethanol hepatotoxicity despite of a severalfold increase in acetaldehyde concentration in the perfusate. Addition of superoxide dismutase or catalase clearly suppressed the ethanol-induced release of GPT and SDH, suggesting that 02∼ and H20, are involved in this process. Also. chelation of iron ions by means of desferrioxamine displayed a clear inhibitory action, suggesting the involvement of an iron-catalyzed Haber-WeiB-reaction leading to the formation of OH radicals in the hepatotoxic response to ethanol. Our data suggest that during the metabolism of acetaldehyde primary reactive oxygen species ('02∼, H202) are produced which may interact to yield hydroxyl or OH-like radicals, which possibly represent the hepatotoxic principle of ethanol.