Toxicity of chenodeoxycholic acid in the nonhuman primate.
Toxicity of chenodeoxycholic acid in the nonhuman primate.
复制标题
鹅去氧胆酸对非人灵长类动物的毒性。
作者：
K. Morrissey;C. Mcsherry;R. Swarm;W. Nieman;J. Deitrick
目前正在狒狒中研究胆石溶解剂鹅去氧胆酸（CDC）长期治疗的毒理学方面。18只动物，细分为低（20 mg.每公斤每天），增量（18至38毫克。每公斤每天），和高（38毫克。每天每公斤）剂量组每天喂食CDC，持续8至15个月。在此期间，它们保持了良好的外观，健康状况和行为与8只对照动物没有区别。然而，18只喂食CDC的动物中有15只显示每月血清谷氨酰胺转氨酶-血清谷氨酰胺乙酸转氨酶测定值显著升高，所有剂量组的18只动物中有14只在连续肝活检中出现显著的局灶性组织学变化。组织学变化与石胆酸毒性相似，并与鹅去氧胆酸百分比升高相关，特别是与CDC喂养动物胆囊胆汁中的石胆酸（8 - 14%）相关。少数CDC喂养的动物显示组织学变化，而无酶变化，反之亦然。到目前为止，没有一个局灶性肝病变出现不可逆性;现在确定持续的CDC喂养是否会导致进展、稳定或消退还为时过早。需要对接受鹅去氧胆酸的人类受试者进行更密切的监测。
Toxicologic aspects of long-term therapy with the gallstone-dissolving agent, chenodeoxycholic acid (CDC) are under study in the baboon. Eighteen animals, subdivided into low (20 mg. per kilogram per day), incremental (18 to 38 mg. per kilogram per day), and high (38 mg. per kilogram per day) dose groups were fed CDC daily for 8 to 15 months. During that period they maintained on appearance of excellent, unchanged health and behavior indistinguishable from that of eight control animals. However, 15 of the 18 CDC-fed animals showed significant elevations of monthly serum glutamic pyruvic transaminase-serum glutamic oxalacetic transaminase determinations, and 14 of the 18, from all dose groups, developed significant focal histologic changes in serial liver biopsies. Histologic changes are similar to those described for lithocholic acid toxicity and correlate with an elevated percentage of chenodeoxycholic acid and, particularly, with lithocholic acid (8 to 14 percent) in gallbladder bile of the CDC-fed animals. A few CDC-fed animals showed histologic changes without enzymatic changes and vice versa. To date none of the focal hepatic lesions appears irreversible; it is too early to determine whether continued CDC feeding results in progression, stabilization, or regression of changes. More intensive surveillance of human subjects receiving chenodeoxycholic acid is indicated.