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

Karen Shattuck, A. Radominska-Pyrek, P. Zimniak, E. W. Adcock, R. Lester, J. St Pyrek

Research output: Contribution to journalArticle

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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 matabolites 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 - 1986
Externally publishedYes

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Glucuronides
Bile
Lithocholic Acid
Hydroxyl Radical
Cholestasis
Bile Acids and Salts
Biliary Fistula
Cutaneous Fistula
Sprague Dawley Rats
Acids
24-norlithocholic acid

ASJC Scopus subject areas

  • Hepatology

Cite this

Metabolism of 24-norlithocholic acid in the rat : Formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow. / Shattuck, Karen; Radominska-Pyrek, A.; Zimniak, P.; Adcock, E. W.; Lester, R.; St Pyrek, J.

In: Hepatology, Vol. 6, No. 5, 1986, p. 869-873.

Research output: Contribution to journalArticle

Shattuck, Karen ; Radominska-Pyrek, A. ; Zimniak, P. ; Adcock, E. W. ; Lester, R. ; St Pyrek, J. / Metabolism of 24-norlithocholic acid in the rat : Formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow. In: Hepatology. 1986 ; Vol. 6, No. 5. pp. 869-873.
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AU - Lester, R.

AU - St Pyrek, J.

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N2 - 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 matabolites 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%).

AB - 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 matabolites 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%).

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