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

Authors

  • Karen E. Shattuck M.D.,

    Corresponding author
    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
    • The University of Texas Medical School, Department of Pediatrics, P.O. Box 20708, Houston, Texas 77225
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  • Anna Radominska-Pyrek,

    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
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  • Piotr Zimniak,

    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
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  • Eugene W. Adcock,

    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
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  • Roger Lester,

    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
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  • Jan St. Pyrek

    1. The University of Texas Health Science Center at Houston, P.O. Box 20708, Houston, Texas 77225 and Biochemistry Department, Rice University, Houston, Texas 77251
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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 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%).

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