Role of biotransformation in the potentiation of halocarbon hepatotoxicity by 2,5-hexanedione.
2,5-Hexanedione (2,5-HD) pretreatment potentiated CHCl3-induced hepatotoxicity. 2,5-HD significantly increased hepatic cytochrome P-450, NADPH cytochrome c reductase, aniline hydroxylation, p-nitroanisole O-demethylation, and aminopyrine N-demethylation in both male and female mice. 2,5-HD pretreatment potentiated CHCl3-induced centrilobular necrosis and increased serum alanine amino transferase (ALT) activity by 20 times more than CHCl3 alone. Similarly, 2,5-HD pretreatment potentiated CDCl3-induced hepatotoxicity as well as CCl4-induced hepatotoxicity in male mice, but did not potentiate trichloroethylene-, 1,1,2-trichloroethane-, or perchloroethylene-induced hepatotoxicity. In female mice, 2,5-HD pretreatment potentiated CHCl3- and CDCl3-induced hepatotoxicity as well as trichloroethylene-, 1,1,2-trichloroethane-, and carbon tetrachloride-induced hepatotoxicity, but not perchloroethylene-induced hepatotoxicity. 2,5-HD pretreatment had no preferential effect on either CHCl3- or CDCl3-induced hepatotoxicity in females. However, phenobarbital pretreatment did differentiate CHCl3- and CDCl3-induced hepatotoxicity in females. 2,5-HD-induced potentiation of halocarbon hepatotoxicity is sex dependent.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001711:Biotransformation; D002725:Chloroform / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004347:Drug Interactions; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006588:Hexanones / Q000494:pharmacology*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D012737:Sex Factors
D006588:Hexanones; D006843:Hydrocarbons, Chlorinated; D007659:Ketones; D002725:Chloroform; D003577:Cytochrome P-450 Enzyme System; C011269:2,5-hexanedione; D006899:Mixed Function Oxygenases; D009245:NADH Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione