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Lithocholate glucuronide is a cholestatic agent.

D G Oelberg, M V Chari, J M Little

    The Journal of Clinical Investigation
    |June 1, 1984
    PubMed
    Summary
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    Lithocholate glucuronide, a compound found in cholestatic syndromes, causes cholestasis similar to lithocholic acid. This study details its excretion and cholestatic effects in rats, revealing rapid bile secretion and dose-dependent cholestasis.

    Area of Science:

    • Hepatology and Gastroenterology
    • Bile Acid Metabolism
    • Pharmacology

    Background:

    • Lithocholic acid derivatives are known cholestatic agents.
    • Lithocholate glucuronide is detected in patients with cholestatic syndromes.
    • Its metabolism, excretion, and cholestatic potential are poorly understood.

    Purpose of the Study:

    • To synthesize and characterize lithocholate glucuronide.
    • To investigate its aqueous solubility and precipitation properties.
    • To determine its metabolism, excretion, and cholestatic effects in vivo.

    Main Methods:

    • Synthesis and radiolabeling of [3 beta-3H]lithocholate 3-O-beta-D-glucuronide.
    • Determination of aqueous solubility and calcium ion precipitation.

    Related Experiment Videos

  • Administration to rats with external biliary fistulas to study biliary excretion.
  • Infusion studies to assess cholestasis induction and bile flow changes.

    • Main Results:

    • Lithocholate glucuronide has higher aqueous solubility than lithocholic acid.
    • It is rapidly secreted in bile in rats (89.1% within 20h), primarily as the parent compound.
    • Milligram doses induce dose-dependent cholestasis, with rapid reduction in bile flow.
    • Cholestasis leads to altered excretion patterns and wider tissue distribution of the compound.

    Conclusions:

    • Lithocholate glucuronide is efficiently excreted via bile in rats.
    • It exerts significant cholestatic effects comparable to unconjugated lithocholic acid.
    • Its rapid induction of cholestasis highlights its clinical relevance in cholestatic syndromes.