Ursodeoxycholate reduces cholate biosynthesis rate and pool size in CFTRS/S mice

F.A. Bodewes, M. Wouthuyzen-Bakker, M. Bijvelds, H.R. De Jonge, H.J. Verkade

    Research output: Contribution to journalMeeting AbstractAcademic

    Abstract

    Objectives and Study: Ursodeoxycholate (UDCA) is used as treatment for cystic fibrosis liver disease (CFLD). It is hypothesized that the supposed therapeutic action of UDCA in CF conditions is either mediated via its choleretic activity or via effects on bile salt metabolism. In CF conditions, however, the effects of UDCA on biliary bile salt composition and on the enterohepatic circulation of bile salts have remained unclear. We evaluated, in Cftr knockout mice and wild type controls, the effects of UDCA treatment on the biliary bile salt composition and on the biosynthesis rate and pool size of cholate (CA), which is proportionally the major hydrophobic bile salt in mouse and man. Methods: Cftr-/-and control mice were either fed standard or treated with UDCA enriched chow (0.5% wt/wt) for 3 weeks. We characterized biliary bile salt composition after gallbladder cannulation and determined the CA synthesis rate and bile salt pool size using a microscale stable isotope dilution technique. Results: In non UDCA treated Cftr-/-mice the fractional biliary CA content was significantly higher compared to controls (61% vs. 46%, resp.; P
    Original languageEnglish
    Pages (from-to)E81
    Number of pages1
    JournalJournal of Pediatric Gastroenterology and Nutrition
    Volume52
    DOIs
    Publication statusPublished - 1-Jun-2011

    Keywords

    • ursodeoxycholic acid
    • cholic acid
    • bile salt
    • stable isotope
    • choleretic agent
    • society
    • mouse
    • biosynthesis
    • nutrition
    • gastroenterology
    • wild type
    • synthesis
    • metabolism
    • human
    • liver fibrosis
    • liver disease
    • therapy
    • cystic fibrosis
    • enterohepatic circulation
    • mouse mutant
    • knockout mouse
    • male
    • gallbladder
    • cannulation
    • dilution

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