Hepatic toxicity in the rhesus monkey treated with chenodeoxycholic acid for 6 months: biochemical and ultrastructural studies.
Hepatic toxicity in the rhesus monkey treated with chenodeoxycholic acid for 6 months: biochemical and ultrastructural studies.
复制标题
用鹅去氧胆酸治疗 6 个月的恒河猴的肝毒性：生化和超微结构研究。
DOI：
10.1016/s0016-5085(76)80409-x
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发表时间：
1976
期刊：
影响因子：
29.4
通讯作者：
E. Mosbach
中科院分区：
文献类型：
--
作者：
H. Dyrszka;G. Salen;F. G. Zaki;T. Chen;E. Mosbach
在人体中长期给予鹅去氧胆酸必须谨慎，因为鹅去氧胆酸在各种动物（包括灵长类动物）中引起肝损伤。为研究鹅去氧胆酸（10、40和100 mg/kg/d）对22只恒河猴肝功能和形态、胆汁胆汁酸组成和变化可逆性的影响。以40和100 mg/kg/天剂量给药6个月后，胆管增生、门脉道炎症和纤维化、胆小管泡形成和滑面内质网肥大与血清草酰乙酸转氨酶、谷氨酸转氨酶和亮氨酸氨肽酶水平升高相关。在胆汁中，鹅去氧胆酸及其细菌代谢产物石胆酸的比例分别上升至约85%和10%。鹅去氧胆酸停药3个月后，尽管胆汁胆汁酸组成恢复正常，但一些动物的肝脏形态学病变仍持续存在。在10 mg/kg/天给药组动物中未观察到肝脏异常。研究结果表明，恒河猴长期接受高剂量鹅去氧胆酸治疗会导致严重的肝脏组织学病变，在停止胆汁酸治疗后可能会持续存在。
The long term administration of chenodeoxycholic acid in man has to be regarded with caution because chenodeoxycholic acid has caused liver damage in various species of animals, including primates. To study the effect of three doses of chenodeoxycholic acid (10, 40, and 100 mg per kg per day) on hepatic function and morphology, biliary bile acid composition and the reversibility of changes were investigated in 22 rhesus monkeys. After 6 months of treatment with 40 and 100 mg per kg per day, bile duct proliferation, portal tract inflammation and fibrosis, bile canalicular bleb formation, and hypertrophy of the smooth endoplasmic reticulum were associated with elevated serum levels of oxaloacetic transaminase, glutamic pyruvic transaminase, and leucine aminopeptidase. In the bile, the proportion of chenodeoxycholic acid and its bacterial metabolite, lithocholic acid, rose to approximately 85 and 10% of the total bile acids. After chenodeoxycholic acid was withdrawn for 3 months, the hepatic morphological lesions persisted in some animals although biliary bile acid composition returned to normal. No hepatic abnormalities were seen in the animals treated with 10 mg per kg per day. The findings suggest that long term treatment of rhesus monkeys with high doses of chenodeoxycholic acid results in severe hepatic histological lesions that can persist after discontinuation of the bile acid.