Abstract

The effect of pyrazole on 1) the in vivo metabolism of ethanol and isopropanol and 2) the ethanol and isopropanol-induced potentiation of CCl₄ hepatotoxicity was studied in rats. Pyrazole delayed the elimination of ethanol. Pyrazole plus ethanol, 18 hours prior to a challenging dose of CCl₄, yielded serum glutamic pyruvic transaminase activities that were 6-fold greater than those observed with ethanol plus CCl₄, with hepatic glucose-6-phosphatase activity also reflecting enhanced toxicity. Acetaldehyde did not display the ability to potentiate CCl₄ hepatotoxicity. Pyrazole markedly enhanced the slight augmentation of CCl₄ hepatotoxicity produced by 1-butanol 18 hours prior to CCl₄. Blood isopropanol concentrations declined more slowly than those of ethanol. With the decline of isopropanol, there was a rise in blood acetone concentrations, the maximum occurring 7 to 10 hours after administration of isopropanol. Pyrazole, 15 minutes prior to isopropanol, produced a delay in the rate of isopropanol elimination, with a concomitant decrease in the rate of acetone formation. Pyrazole, 15 minutes prior to isopropanol, diminished the enhanced response of CCl₄ to isopropanol, with serum glutamic pyruvic transaminase levels reduced to 40% of that found for isopropanol and CCL₄; triglyceride levels also reflected reduced hepatotoxicity. An 18-hour pretreatment with acetone enhanced CCl₄ toxicity (elevated serum glutamic pyruvic transaminase activity). These results indicate that the potentiation observed after ethanol is associated with nonmetabolized ethanol, while acetone derived during the in vivo oxidation of isopropanol appears to contribute to the response observed after isopropanol.