Metabolism of 24‐norlithocholic acid in the rat: Formation of hydroxyl‐ and carboxyl‐linked glucuronides and effect on bile flow

Karen E. Shattuck, Anna Radominska‐Pyrek, Piotr Zimniak, Eugene W. Adcock, Roger Lester, Jan St Pyrek

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 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%).

Original languageEnglish (US)
Pages (from-to)869-873
Number of pages5
JournalHepatology
Volume6
Issue number5
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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