Leuschner U, Schneider M, Loos R, Kurtz W
Res Exp Med (Berl). 1977 Aug 16;171(1):41-55. doi: 10.1007/BF01851587.
Light- and electron microscopic alterations of the liver and light microscopic findings in the gastro intestinal tract, the kidney and adrenal gland of 80 female Wistar-Rats under CDCA therapy are reported. CDCA was applied by means of an endopharnygeal tube over a period of 60 days in doses of 150, 250, 500 and 1000 mg/kg body weight. The organs were examined at different times. We compared the achieved findings to results obtained already beforehand by light- and electron microscopy after application of 20, 50 and 90 mg/kg body weight and day: Up to a dosage of 90 mg/kg morphological changes of the liver were only visible electron optically, from 150 mg/kg onward they could be seen light optically as well. After 60 days a cirrhosis-like picture had developed. The lethal dose was established at 1000 mg/kg. There were no pathological alterations in the gastrointestinal tract and no definite ones in the kidneys. The adrenal glands were unchanged.--Since there are in the rats, in spite of potent mechanisms of detoxication of CDCA and LCA, even at low doses morphological alterations to be seen, the existence of other toxic, at this moment still unknown metabolites is being discussed.
报告了80只接受熊去氧胆酸(CDCA)治疗的雌性Wistar大鼠肝脏的光镜和电镜改变以及胃肠道、肾脏和肾上腺的光镜检查结果。通过咽内管以150、250、500和1000毫克/千克体重的剂量给予CDCA,持续60天。在不同时间对器官进行检查。我们将所获得的结果与之前在给予20、50和90毫克/千克体重/天的剂量后通过光镜和电镜获得的结果进行了比较:剂量高达90毫克/千克时,肝脏的形态学改变仅在电镜下可见,从150毫克/千克起,在光镜下也可见。60天后出现了类似肝硬化的图像。致死剂量确定为1000毫克/千克。胃肠道无病理改变,肾脏无明确改变。肾上腺无变化。——由于尽管大鼠体内存在强大的CDCA和LCA解毒机制,但即使在低剂量下也能观察到形态学改变,因此正在讨论是否存在其他有毒的、目前仍未知的代谢产物。