PREVENTION OF ACETAMINOPHEN-INDUCED HEPATOTOXICITY BY ACUTE ETHANOL ADMINISTRATION IN THE RAT - COMPARISON WITH CARBON TETRACHLORIDE-INDUCED HEPATOTOXICITY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (3) , 805-810
Abstract
Acetaminophen-induced hepatotoxicity in the presence of ethanol has not been studied. To evulate the effect of acute ethanol administration on the hepatotoxicity of acetaminophen, young male Sprague-Dawley rats (90-130 g) were fasted for 18 h and given ethanol (6 g/kg orally) or saline. Six hours after treatment, the rats were injected with acetaminophen (0.5-1.0 g/kg i.p.). Rats were given ethanol (3 g/kg orally) or saline and acetaminophen (1 g/kg i.p.) concomitantly. In both groups, acetaminophen produced hepatic damage in saline controls; ethanol treatment prevented the hepatotoxicity as judged by serum enzyme activities, hepatic cytochrome P-450 content and liver histology. In 3-methylcholanthrene-treated animals, acetaminophen (0.25 g/kg)-induced hepatic damage was exacerbated; ethanol treatment (6 g/kg orally) apparently prevented the hepatotoxicity of acetaminophen. CCl4-induced hepatotoxicity (0.1-0.5 ml/kg i.p.) was increased by acute ethanol administration 6 h before drug injection, suggesting that the interaction of ethanol- and drug-induced hepatotoxicity was complex. Because acetaminophen produced hepatic injury after its biotransformation to reactive metabolite(s) by mixed-function oxidation, and because ethanol inhibited drug oxidation, it can be postulated that ethanol inhibited the biotransformation of acetaminophen to reactive metabolite(s), resulting in the prevention of hepatotoxicity.