Potentiation of CCl4 hepatotoxicity in rats by a metabolite of 2-butanone: 2,3-butanediol.
The role of ketaone metabolism in 2-butanone-induced potentiaion of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. The blood concentrations of 2-butanol, 3-hydroxy-2-butanone and 2,3-butanediol detected 4 h after dosing were 3.2 mg/100 ml, 2.4 mg/100 ml and 8.6 mg/100 ml, respectively. Eighteen hours after 2-butanone, the concentration of 2,3-butanediol rose to 25.6 mg/100 ml, while the concentrations of 2-butanol and 3-hydroxy-2-butanone declined to 0.6 mg/100 ml and 1.4 mg/100 ml, respectively. A 16-h pretreatment with either 2-butanone (2.1 ml/kg, p.o.) or 2,3-butanediol (2.12 ml/kg, p.o.) markedly enhanced the hepatotoxic response to CCl4 (0.1 ml/kg, i.p.), as measured by serum glutamic pyruvic transaminase activity and hepatic triglyceride content. In vivo, limited formation of 3-hydroxy-2-butanone occurred after this dose of 2,3-butanediol. These data suggest that the production of 3-hydroxy-2-butanone and 2,3-butanediol via 2-butanone metabolism may participate in the augmented necrogenic effect of CCl4 seen after pretreatment with 2-butanone.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002074:Butanones / Q000097:blood / Q000494:pharmacology; D002072:Butylene Glycols / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002849:Chromatography, Gas; D004357:Drug Synergism; D008297:Male; D051381:Rats; D013997:Time Factors
D002074:Butanones; D002072:Butylene Glycols; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase