Kurebe M, Yokota M, Kawaoto H, Niizato T, Watanabe H, Hayasaka H
Jpn J Antibiot. 1984 May;37(5):890-917.
The chronic toxicity of MT-141 was studied in male and female Wistar rats with 182-time intramuscular injections of 50, 100, 200, 400, 800 and 1,600 mg/kg/day and the following results were obtained. MT-141 at all dosage levels caused no lethal effect on rats. However, it induced local inflammatory changes at the site of injection, such as hemorrhage, infiltration of round cells and fibrosis particularly at high doses. MT-141 at a high dose of 1,600 mg/kg/day decreased the gain of body weights in male rats but not in female rats. MT-141 increased the water intake in male and female rats from 8th day till last day after treatments with the doses more than 800 mg/kg/day. This compound also softened the feces and distended the cecum. MT-141 at the highest dosage level of 1,600 mg/kg/day increased the weight of kidney in male and female rats. Electron-microscopic findings revealed dissociation of basal infolding and dilatation of endoplasmic reticulum in renal epithelial cells of rats treated with the doses more than 800 mg/kg/day. These results suggest that MT-141 may induce renal toxicity in rats at these doses. The administration of MT-141 changed some toxicological parameters in gross and histopathological examinations and analyses of blood, serum and urine. However, the changes were accidental, independent on the dose and within physiological variations. It is concluded from above-mentioned results that the maximal "no effective" dose of MT-141 is 400 mg/kg/day in male and female rats.
通过对雄性和雌性Wistar大鼠进行182次肌肉注射，剂量分别为50、100、200、400、800和1600mg/kg/天，研究了MT - 141的慢性毒性，结果如下。所有剂量水平的MT - 141对大鼠均无致死作用。然而，它在注射部位引起局部炎症变化，如出血、圆形细胞浸润和纤维化，尤其是在高剂量时。高剂量1600mg/kg/天的MT - 141使雄性大鼠体重增加减少，但对雌性大鼠无此影响。MT - 141在剂量超过800mg/kg/天处理后，从第8天直至最后一天增加了雄性和雌性大鼠的饮水量。该化合物还使粪便变软并使盲肠扩张。最高剂量水平1600mg/kg/天的MT - 141使雄性和雌性大鼠的肾脏重量增加。电子显微镜检查结果显示，剂量超过800mg/kg/天处理的大鼠肾上皮细胞中基底褶皱解离和内质网扩张。这些结果表明，在这些剂量下MT - 141可能诱导大鼠肾毒性。MT - 141的给药在大体和组织病理学检查以及血液、血清和尿液分析中改变了一些毒理学参数。然而，这些变化是偶然的，与剂量无关且在生理变异范围内。从上述结果得出结论，MT - 141在雄性和雌性大鼠中的最大“无效应”剂量为400mg/kg/天。
