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Metabolism of 24‐norlithocholic acid in the rat: Formation of hydroxyl‐ and carboxyl‐linked glucuronides and effect on bile flow
Author(s) -
Shattuck Karen E.,
RadominskaPyrek Anna,
Zimniak Piotr,
Adcock Eugene W.,
Lester Roger,
Pyrek Jan St.
Publication year - 1986
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840060511
Subject(s) - lithocholic acid , chemistry , bile acid , metabolism , cholestasis , glucuronide , metabolite , glucuronic acid , glucuronates , biochemistry , medicine , polysaccharide
24‐Norlithocholic (3α‐hydroxy‐24‐nor‐5β‐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, 3β‐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 C 23 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%).