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

✍ Scribed by Karen E. Shattuck; Anna Radominska-Pyrek; Piotr Zimniak; Eugene W. Adcock; Roger Lester; Jan St. Pyrek

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 596 KB
• Volume: 6
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840060511

✦ Synopsis

24-Norlithocholic

(3a-hydroxy-24-nor-5/3-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#?-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-, diand trihydroxylated CpD 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 3hydroxyl and carboxyl groups, was detected (11%).

Principal Ca4 bile acids (BA), exemplified by cholic, chenodeoxycholic and deoxycholic acids, are efficiently conjugated with amino acids before their biliary secretion. On the other hand, short chain C20-C23 BA are metabolized by pathways other t h a n amidation. Of t h e common C2* BA, lithocholic acid, a minor monohydroxylated constituent of human a n d rat bile (1-4), is generally considered t o be t h e most cholestatic when administered in large amounts t o experimental animals (9)(11).

In the present study, we therefore examined t h e metabolism of the lower homologue of lithocholic acid, 24norlithocholic acid [(NLC) C?:;], using rats prepared with a biliary fistula.

MATERIALS AND METHODS

Experimental Design.

[ 3b-'HI -3n-hydroxy-24-nor-5& cholan-23-oic (["HINLC) acid, synthesized as described earlier