Potentiation of lithocholic-acid-induced cholestasis by methyl isobutyl ketone. 1992

L D Joseph, and I M Yousef, and G L Plaa, and M Sharkawi
Department of Pharmacology, University of Montreal, Canada.

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.

UI MeSH Term Description Entries
D008095 Lithocholic Acid A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. Lithocholate,Isolithocholic Acid,Acid, Isolithocholic,Acid, Lithocholic
D008297 Male Males
D008742 Methyl n-Butyl Ketone An industrial solvent which causes nervous system degeneration. MBK is an acronym often used to refer to it. 2-Hexanone,Butylmethyl Ketone,Hexan-2-one,2 Hexanone,Hexan 2 one,Ketone, Butylmethyl,Ketone, Methyl n-Butyl,Methyl n Butyl Ketone,n-Butyl Ketone, Methyl
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002780 Cholestasis, Intrahepatic Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC). Bile Duct Obstruction, Intrahepatic,Biliary Stasis, Intrahepatic,Intrahepatic Cholestasis,Biliary Stases, Intrahepatic,Cholestases, Intrahepatic,Intrahepatic Biliary Stases,Intrahepatic Biliary Stasis,Intrahepatic Cholestases
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001647 Bile Acids and Salts Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. Bile Acid,Bile Salt,Bile Salts,Bile Acids,Acid, Bile,Acids, Bile,Salt, Bile,Salts, Bile

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