Wagner V R, Oehlert W, Schmidt U
Arzneimittelforschung. 1975 Mar;25(3):397-402.
The present paper deals with the toxic effect of a mycotoxin of the group of epidithio-dioxopiperazines: cyclo-sarcosyl-sarcosin-epitetrasulfide, particularly upon the liver of guinea-pigs and rats. The sporidesmines, related to the compound tested, cause chronic obstructive cholangitis characteristic of a disease in sheep endemic in New Zealand. This type of cholangitis was attempted to be reproduced in order to establish an experimental model of producing biliary cirrhosis in animals. The acute and subacute LD50 in rats and guinea-pigs were determined intraperitoneally and intragastrally. In neither mode of application nor in short-term nor in chronic test could we find any specific, dose dependent changes of bile ducts. Merely, parenteral administration of lethal doses led to unspecific subcapsular liver necroses obviously due to direct diffusion of the toxic agent. The discrepancy between the efficacy of the toxic grass in New Zealand and the substance tested in the study is discussed.
本文探讨了环二硫代二氧哌嗪类霉菌毒素——环肌氨酸 - 肌氨酸 - 表四硫化物的毒性作用,尤其是对豚鼠和大鼠肝脏的影响。与所测试化合物相关的孢霉菌素会引发慢性阻塞性胆管炎,这是新西兰绵羊一种地方病的特征。为了建立动物胆汁性肝硬化的实验模型,尝试重现这种类型的胆管炎。通过腹腔注射和灌胃测定了大鼠和豚鼠的急性和亚急性半数致死剂量(LD50)。无论是给药方式,还是短期或长期试验,我们都未发现胆管有任何特定的、剂量依赖性变化。仅仅是注射致死剂量会导致非特异性的肝包膜下坏死,这显然是由于有毒物质的直接扩散所致。文中还讨论了新西兰有毒牧草的效力与本研究中所测试物质之间的差异。