The participation of 2-butanone in 2-butanol-induced potentiation of carbon tetrachloride hepatotoxicity.
The role of alcohol metabolism in 2-butanol-induced potentiation of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. Animals were sacrificed at various times after the administration of 2-butanol (2.2 ml/kg p.o.) 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 hours. With the decline of 2-butanol concentrations, there was a rise in 2-butanone blood concentrations with 43 mg/100 ml detected at 1 hour and a maximum of 105 mg/100 ml detected 4 hours after the administration of the alcohol. A 16-hour pretreatment with either 2-butanol (2.2 ml/kg p.o.) or 2-butanone (1.87 ml/kg p.o.) 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. The results indicate that 2-butanone production via the oxidation of 2-butanol appears to contribute to the marked response of 2-butanol.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D013997:Time Factors
D000410:Alanine Transaminase