Palmer R H, McSherry C K
J Lab Clin Med. 1982 Apr;99(4):533-8.
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.
对大多数物种施用鹅去氧胆酸盐会导致肝脏损伤，推测这是由于由鹅去氧胆酸盐形成的石胆酸盐所致。人类相对未能出现类似损伤可能是由于石胆酸盐代谢的差异，主要是石胆酸盐的广泛硫酸化和快速消除。为了进一步深入了解对鹅去氧胆酸盐反应的物种差异，在四只具有正常胆囊的雌性狒狒中研究了14C-石胆酸盐的代谢。在两只接受鹅去氧胆酸盐的动物和两只对照动物中，研究了胆汁中代谢物的分布以及14C-石胆酸盐在牛磺酸和甘氨酸结合池中动力学。只有10%的代谢物被硫酸化，另外10%以极性更强的化合物形式出现；治疗组和对照组动物之间没有差异。动力学研究表明，治疗组动物的输入量和池大小比对照组大两到三倍。分数周转率比人类或胆囊切除的猴子慢得多，池大小要大得多。这些研究结果是首次在具有正常胆囊的动物中进行的，支持了硫酸化在保护人类免受石胆酸盐毒性方面起重要作用的假设。鹅去氧胆酸盐转化为石胆酸盐并被吸收进入循环池的程度也可能存在差异。
