Abstract
Acetaminophen-induced hepatotoxicity in the presence of ethanol has not been studied. To evaluate the effect of acute ethanol administration on the hepatoxicity of acetaminophen, young male Sprague-Dawley rats (b. wt. 90--130 g) were fasted for 18 hr and were given ethanol (6 g/kg p.o.) or saline. Six hours after this treatment, the rats were injected with acetaminophen (0.5--1.0 g/kg i.p.). In another group, rats were given ethanol (3 g/kg p.o.) or saline and acetaminophen (1 g/kg i.p.) concomitantly. In both groups, acetaminophen produced hepatic damage in saline controls, whereas ethanol treatment prevented the hepatoxicity 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, whereas again ethanol treatment (6 g/kg p.o.) apparently prevented the hepatotoxicity of acetaminophen. In contrast, carbon tetrachloride-induced hepatotoxicity (0.1--0.5 ml/kg i.p.) was markedly increased by acute ethanol administration 6 hr before the drug injection, suggesting that the interaction of ethanol- and drug-induced hepatotoxicity is complex. Because acetaminophen has been shown to produce hepatic injury after its biotransformation to reactive metabolite(s) by mixed-function oxidation, and because ethanol inhibits drug oxidation, it can be postulated that ethanol inhibits the biotransformation of acetaminophen to reactive metabolite(s) resulting in the prevention of hepatotoxicity.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|