Potentiation of lithocholic-acid-induced cholestasis by methyl isobutyl ketone.
Methyl isobutyl ketone was found to potentiate intrahepatic cholestasis induced by taurolithocholate and the combination of manganese-bilirubin. The aim of this study was to elucidate the mechanism of this potentiation using the lithocholate-induced cholestasis model. Male rats were given methyl isobutyl ketone 7.5 mumol/kg body wt. daily for 3 days. The effect of this treatment on lithocholate-induced cholestasis, bile formation and taurocholic acid transport was examined. The data showed that methyl isobutyl ketone treatment potentiated lithocholate-induced cholestasis and reduced significantly bile salt, phospholipid and cholesterol secretion rates as well as the transport maximum of taurocholic acid. It is suggested that methyl isobutyl ketone potentiates lithocholate-induced cholestasis by reducing the bile salt pool and interfering with the haptic secretion rate of bile salts.
Joseph
L D
LD
Department of Pharmacology, University of Montreal, Canada.
Yousef
I M
IM
Plaa
G L
GL
Sharkawi
M
M
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001648:Bile Canaliculi / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced*; D004357:Drug Synergism; D008095:Lithocholic Acid / Q000633:toxicity*; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D008095:Lithocholic Acid; D008742:Methyl n-Butyl Ketone; C005458:methyl isobutyl ketone