In vivo toxicological evaluation of Anisomycin
In vivo toxicological evaluation of Anisomycin
复制标题
茴香霉素的体内毒理学评价。
DOI：
10.1016/j.toxlet.2011.10.001
复制
发表时间：
2012-01-05
影响因子：
3.5
通讯作者：
Liu Jing
中科院分区：
文献类型：
--
作者：
Tang Zhengle;Xing Feiyue;Liu Jing
茴香霉素是一种从灰色链霉菌中分离出来的吡咯烷类抗生素。最近的研究表明，茴香霉素作为一种新型免疫抑制剂上级环孢霉素A（J. Immunother. 31，858-870，2008）。为了对茴香霉素进行毒理学评价，进行了小鼠急性毒性和连续4周静脉毒性试验。对外周血淋巴细胞的IC_（50）值为25.44 ng/ml。茴香霉素的LD 50计算值为119.64 mg/kg。通过小鼠尾静脉每隔一天静脉注射总剂量为5、15、30和60 mg/kg/小鼠的茴香霉素，持续4周。仅高剂量组有3只小鼠死亡，体重明显下降。器官指数的统计学显著性变化包括脾脏、肝脏、肺和脑与体重的比值增加，以及胸腺与体重的比值降低。临床生化参数的变化包括天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）活性升高以及葡萄糖（GLU）活性降低。肺、肝、肾组织出现明显炎症反应，脾脏巨核细胞数量和体积明显增多。茴香霉素不诱导外周血微核形成，但增加骨髓嗜多染红细胞微核数和精子畸变。然而，上述异常变化仅发生在高剂量茴香霉素处理的小鼠中。这些结果表明，虽然茴香霉素在有效治疗剂量下没有明显的副作用，但其过量可能导致毒性，特别是肺、肾和肝毒性。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus. Recent studies have shown that Anisomycin as a novel immunosuppressive agent is superior to Cyclosporine A(J. Immunother. 31, 858-870, 2008). In order to make toxicological evaluation of Anisomycin, acute and four-week continuously intravenous toxicity studies were performed in mice. IC50 value tested on peripheral lymphocytes was 25.44 ng/ml. The calculated LD50 for Anisomycin was 119.64 mg/kg. The mice were intravenously injected through mouse tail vein with a total dose of 5, 15, 30 and 60 mg/kg/mice of Anisomycin every other day for 4 weeks. Just in the high-dose mice, death of three mice happened and body weight of the mice was significantly decreased. Statistically significant changes in organ index included increases in ratios of the spleen, liver, lung and brain to the body weight, and decrease in ratio of the thymus to the body weight. Changes in clinical biochemistry parameters included increases in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and decreases in the glucose (GLU) activity. The distinct inflammation appeared in the lung, liver and kidney, and the number and size of megakaryocytes in the spleen were significantly increased. Anisomycin did not induce formation of the peripheral blood micronucleus, but increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm aberrations. However, the above aberrant changes occurred only in the mice treated with the high-dose Anisomycin. These results indicate that although Anisomycin has no significant side effects at effectively therapeutic doses, its over-dosage may lead to toxicity, particularly pulmo-, nephro- and hepato-toxicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.