PARTICIPATION OF 2-BUTANONE IN 2-BUTANOL-INDUCED POTENTIATION OF CARBON-TETRACHLORIDE HEPATOTOXICITY

Abstract

The role of alcohol metabolism in 2-butanol-induced potentiation of CCl4 hepatotoxicity was studied in rats. Animals were sacrificed at various times after the administration of 2-butanol (2.2 ml/kg orally) for the determination of blood 2-butanol and 2-butanone concentrations by gas chromatographic analysis. 2-Butanol exhibited an apparent elimination half-life of 2.5 h. With the decline of 2-butanol concentrations, there was a rise in 2-butanone blood concentrations with 43 mg/100 ml detected at 1 h and a maximum of 105 mg/100 ml detected 4 h after the administration of the alcohol. A 16-h pretreatment with either 2-butanol (2.2 ml/kg orally) or 2-butanone (1.87 ml/kg orally) markedly enhanced the hepatotoxic response of CCl4 (0.1 ml/kg i.p.) as measured by serum glutamic pyruvic transaminase activity, hepatic glucose-6-phosphatase activity and triglyceride content. The enhanced hepatotoxicity produced by 2-butanol was not significantly different from that produced by 2-butanone. The potentiation of CCl4 hepatotoxicity by both agents was substantiated morphologically. 2-Butanone production via the oxidation of 2-butanol appears to contribute to the marked response of 2-butanol.