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Urinary excretion of lithocholic acid and its conjugates by the bile duct–ligated rat
Author(s) -
Little Joanna M.,
Zimniak Piotr,
Radominska Anna,
Lester Roger,
Lehman Paul
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840140419
Subject(s) - lithocholic acid , urine , chemistry , cholic acid , glucuronide , bile acid , excretion , chromatography , biochemistry , medicine
The 3‐O‐glucuronide of lithocholic acid has been shown to be a potent cholestatic agent in rats. However, even after the onset of lithocholic acid glucuronide–induced cholestasis, little of the administered material was recovered in urine. To determine whether this phenomenon was related to the steroid moiety or the form of conjugation, small doses of radiolabeled lithocholic acid glucuronide, lithocholic acid, taurolithocholic acid and/or lithocholic acid sulfate were administered to rats with ligated bile ducts. Urinary excretion of isotope was followed for 24 hr and urinary metabolites of the administered compounds were identified by thin‐layer chromatography. Lithocholic and taurolithocholic acids were slowly but relatively efficiently excreted in urine with 73% and 91% of the dose, respectively, recovered in urine over 24 hr. More than 80% of the label in urine from animals receiving these two compounds was in the form of taurine‐conjugated β‐muricholic acid. In contrast, lithocholic acid 3‐glucuronide and 3‐sulfate were poorly excreted: 9% and 12% of the administered doses, respectively, were recovered in urine in 24 hr. Of the small amount of label in urine from rats given the glucuronide, 90% was identified as lithocholic and taurolithocholic acid glucuronides. When lithocholic acid sulfate was given, thin‐layer chromatography of urine showed two peaks, which were tentatively identified as tauromurideoxycholic and taurolithocholic acid sulfates. More definitive identification was not possible because of the small amount of the administered dose excreted in urine in these forms. It is apparent from the results that conjugation of the 3‐hydroxy group of lithocholic acid with sulfate or glucuronide severely impairs the additional hydroxylation of the steroid nucleus that is a prerequisite for effective renal excretion, resulting in the retention of these toxic metabolites in the body. (H EPATOLOGY 1991;14:690–695.)