Mamianetti A, Konopka H F, Lago N, Vescina C, Scarlato E, Carducci C N
Departamento Docencia e Investigación Hospital Aeronáutico Central, Capital Federal, Argentina.
Pharmacol Res. 1994 Feb-Mar;29(2):187-95. doi: 10.1016/1043-6618(94)80043-x.
The effects of high doses of ursodeoxycholic acid on bile acid composition and the liver morphology was examined in 60 male Syrian golden hamsters. The animals were allocated to five groups: I, control; II and IV received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 30 days and III and V received 0.5 g and 1 g of ursodeoxycholic acid per 100 g of standard diet respectively over 60 days. Bile acids were determined by high performance liquid chromatography. In all treated groups there was a significant increase in chenodeoxycholic and lithocholic acid in the bile. The mean glyco/tauro ratio was significantly higher than in the control group, reaching values > 1 for individual bile acids, except for lithocholic acid values which remained < 1. Under light microscopy, the livers of the hamsters showed damage which was dose/time related, namely portal inflammatory infiltrate, bile duct proliferation, cholestasis, fat infiltration and necrosis. Electron microscopy revealed pronounced changes starting with microvilli edema and extending to canalicular membrane destruction and necrosis. The changes observed in the relation glyco/tauro lithocholic acids, may be due to defence mechanisms to avoid hepatotoxicity. The hepatotoxicity resulting from ursodeoxycholic acid administration is presumed to be due primarily to lithocholic acid or some lithocholic acid metabolite.
在60只雄性叙利亚金黄地鼠中研究了高剂量熊去氧胆酸对胆汁酸组成和肝脏形态的影响。将动物分为五组：I组为对照组；II组和IV组在30天内分别按每100克标准饮食给予0.5克和1克熊去氧胆酸，III组和V组在60天内分别按每100克标准饮食给予0.5克和1克熊去氧胆酸。通过高效液相色谱法测定胆汁酸。在所有处理组中，胆汁中鹅去氧胆酸和石胆酸均显著增加。糖/牛磺比值显著高于对照组，除石胆酸值仍<1外，个别胆汁酸的值>1。在光学显微镜下，地鼠肝脏显示出与剂量/时间相关的损伤，即门静脉炎性浸润、胆管增生、胆汁淤积、脂肪浸润和坏死。电子显微镜显示出明显变化，始于微绒毛水肿，并扩展至胆小管膜破坏和坏死。在糖/牛磺石胆酸关系中观察到的变化，可能归因于避免肝毒性的防御机制。推测熊去氧胆酸给药导致的肝毒性主要归因于石胆酸或某些石胆酸代谢产物。
