Schwenk M, Hofmann A F, Carlson G L, Carter J A, Coulston F, Greim H
Arch Toxicol. 1978 Apr 27;40(2):109-18. doi: 10.1007/BF01891965.
To characterize the hepatic biotransformation in the chimpanzee of the primary bile acid chenodeoxycholic acid (chenic) and its major bacterial metabolite lithocholic acid (lithocholic) a mixture of trace amounts of 14C-lithocholic and 3H-chenic was injected intravenously into two animals with a bile fistula; the chemical form of radioactivity appearing in bile was inferred using thin layer chromatography. About 80% of chenic, and 70% of lithocholic was recovered in 90 min. Chenic was completely conjugated in bile, appearing predominantly as chenyltaurine (52%) and chenylglycine (37%). An unidentified conjugate (about 11%) was also found. Lithocholic was excreted completely as taurine and glycine conjugates, but the majority (63%) of conjugates was sulfated. Sulfation increased progressively with time, and lithocholylglycine was sulfated more than lithocholyltaurine. We conclude that the chimpanzee is similar to man in that the secondary bile acid lithocholic is efficiently sulfated. The chimpanzee thus differs from the baboon and rhesus monkey which sulfate lithocholic poorly. However, the chimpanzee differs from man and is similar to the baboon and rhesus monkey in showing preferential conjugation of bile acids with taurine. The results imply that hepatotoxicity caused by chenic, which is well documented in the rhesus monkey and baboon and has been related to defective lithocholic sulfation, should not occur in the chimpanzee.
为了表征黑猩猩体内初级胆汁酸鹅去氧胆酸(chenic)及其主要细菌代谢产物石胆酸(lithocholic)的肝脏生物转化情况,将痕量的14C-石胆酸和3H-鹅去氧胆酸的混合物静脉注射到两只患有胆瘘的动物体内;利用薄层色谱法推断胆汁中出现的放射性化学形式。在90分钟内,约80%的鹅去氧胆酸和70%的石胆酸被回收。鹅去氧胆酸在胆汁中完全结合,主要以苯甲酰牛磺酸(52%)和苯甲酰甘氨酸(37%)的形式出现。还发现了一种未鉴定的结合物(约11%)。石胆酸完全以牛磺酸和甘氨酸结合物的形式排泄,但大多数(63%)结合物被硫酸化。硫酸化随时间逐渐增加,石胆酰甘氨酸比石胆酰牛磺酸更易被硫酸化。我们得出结论,黑猩猩与人类相似,即次级胆汁酸石胆酸能有效地被硫酸化。因此,黑猩猩与狒狒和恒河猴不同,后者对石胆酸的硫酸化能力较差。然而,黑猩猩与人类不同,与狒狒和恒河猴相似,胆汁酸优先与牛磺酸结合。结果表明,在恒河猴和狒狒中已充分记录的、与石胆酸硫酸化缺陷有关的鹅去氧胆酸引起的肝毒性,在黑猩猩中不应发生。