Metabolism of 24-norlithocholic acid in the rat: formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow.
24-Norlithocholic (3 alpha-hydroxy-24-nor-5 beta-cholan-23-oic) acid is the lower homologue of lithocholic acid, a potent cholestatic agent. In order to characterize its cholestatic potential and metabolic fate, 3 beta-tritiated 24-norlithocholate was infused intravenously into adult male Sprague-Dawley rats prepared with an external biliary fistula. The results demonstrate that 24-norlithocholate does not induce cholestasis in rats when administered in doses in excess of those necessary for lithocholate to produce cholestasis. Hydroxyl- and carboxyl-linked glucuronides were identified as major metabolites secreted in the bile. Especially noteworthy is the identification of carboxyl-linked glucuronides of mono-, di- and trihydroxylated C23 bile acids. Their total amount (25% of recovered radioactive products) is comparable to that of the hydroxyl-linked glucuronide of 24-norlithocholic acid (41%). In this study, for the first time, a bile acid diglucuronide, substituted both at 3-hydroxyl and carboxyl groups, was detected (11%).
D000818:Animals; D001646:Bile / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism*; D007262:Infusions, Intravenous; D008095:Lithocholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D013057:Spectrum Analysis
D005965:Glucuronates; C048433:24-norlithocholic acid; D008095:Lithocholic Acid