Interaction of Acute Ethanol Administration with Acetaminophen Metabolism and Toxicity in Rats Fed Alcohol Chronically

In rats fed alcohol chronically, acetaminophen induced severe hepatotoxicity as judged by serum enzyme activities, liver histology, and mortality, whereas in both rats fed alcohol chronically and in their pair-fed controls, acute ethanol administration decreased acetaminophen hepatotoxicity. Since acetaminophen hepatotoxicity is increased in rats fed alcohol chronically and acute ethanol has been shown to inhibit the biotransformation of acetaminophen to reactive metabolite(s) by mixed function oxidation, we postulate that acute ethanol administration decreases acetaminophen-induced hepatotoxicity in rats fed alcohol chronically by inhibiting the enhanced production of toxic metabolites.