title: Lithocholate metabolism in baboons fed chenodeoxycholate.
abstract: The administration of chenodeoxycholate to most species results in hepatic lesions presumed to be due to lithocholate formed from chenodeoxycholate. The relative failure of humans to develop similar lesions may be due to differences in lithocholate metabolism, primarily extensive sulfation and rapid elimination of lithocholates. To gain further insight into species differences in response to chenodeoxycholate, the metabolism of 14C-lithocholate was studied in four female baboons with functioning gallbladders. The distribution of metabolites in bile and the kinetics of of 14C-lithocholate in the taurine- and glycine-conjugated pools were studied in two animals receiving chenodeoxycholate and in two controls. Only 10% of the metabolites were sulfated, with an additional 10% occurring as more polar compounds; there was no difference between treated and control animals. Kinetic studies showed inputs and pool sizes that were two to three times greater in treated animals than in controls. Fractional turnover rates were much slower than in humans or cholecystectomized monkeys and pool sizes were much larger. The results of these studies, the first in animals with functioning gallbladders, support the hypothesis that sulfation plays an important role in protecting humans against lithocholate toxicity. There also may be differences in the extent to which chenodeoxycholate is converted to lithocholate and absorbed to enter the circulating pool.
mesh_terms: D000818:Animals; D001646:Bile / Q000032:analysis / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage*; D002855:Chromatography, Thin Layer; D004032:Diet; D005260:Female; D005704:Gallbladder / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007700:Kinetics; D008095:Lithocholic Acid / Q000378:metabolism*; D010215:Papio; D013654:Taurine / Q000378:metabolism
chemical_list: D002635:Chenodeoxycholic Acid; D013654:Taurine; D008095:Lithocholic Acid; D005998:Glycine