Taurolithocholate-induced intrahepatic cholestasis: potentiation by methyl isobutyl ketone and methyl n-butyl ketone in rats.
Haloalkane-induced hepatonecrogenesis can be potentiated by the prior administration of methyl isobutyl ketone (MIBK) and methyl n-butyl ketone (MBK). We investigated the possibility that these ketones could potentiate the cholestasis induced by taurolithocholate (TLC) in rats. Daily ketone pretreatment for 3 or 7 days resulted in an enhancement of the diminution in bile flow observed after TLC challenge. When the ketones were administered without TLC challenge, cholestasis was not observed; in fact, slight increases in bile flow did occur. The data suggest that MIBK may be more effective than MBK as a potentiator. Preliminary experiments with 2,5-hexanedione (HD), a metabolite of MBK and a potent potentiator of haloalkane hepatonecrosis, were included in the study. HD appeared to be a less potent potentiator of TLC-induced cholestasis. Although some ketones can potentiate cholestatic as well as hepatonecrogenic reactions, different mechanisms of action appear to be involved in these two phenomena.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D002779:Cholestasis / Q000139:chemically induced*; D004357:Drug Synergism; D006588:Hexanones / Q000494:pharmacology; D007275:Injections, Intravenous; D007659:Ketones / Q000494:pharmacology*; D008095:Lithocholic Acid / Q000031:analogs & derivatives*; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013658:Taurolithocholic Acid / Q000633:toxicity*
D006588:Hexanones; D007659:Ketones; D013658:Taurolithocholic Acid; D008095:Lithocholic Acid; D008742:Methyl n-Butyl Ketone; C011269:2,5-hexanedione; C005458:methyl isobutyl ketone