Suzuki Y, Sudo J
Department of Toxicology and Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Jpn J Pharmacol. 1989 Jan;49(1):43-51. doi: 10.1254/jjp.49.43.
To elucidate the toxic and protective mechanisms responsible for cephaloridine (CER)-induced nephrotoxicity, changes in renal formation of malondialdehyde and renal activities of xanthine oxidase, superoxide dismutase and catalase were mainly investigated for 15 days in rats that received single intravenous injections of CER in doses of 100 and 1,000 mg/kg body weight. In the 100 mg/kg group, the above items determined remained within the control levels. In the 1,000 mg/kg group, renal formation of malondialdehyde was observed to be accelerated with the following two stages: highly in the early stage (the 3rd hour to the 2nd day, especially at the 3rd hour) and more highly in the late stage (the 2nd to the 7th day). Concerning the other items determined, significantly different changes were hardly observed in the 1,000 mg/kg group within the 12th hour of the early stage, while the rises in renal activities of xanthine oxidase and falls in renal activities of superoxide dismutase and catalase were observed in the late stage. These results suggested that the increment in malondialdehyde formation in the late stage might be explained enzymatically by both the rises in the activities of xanthine oxidase and the declines in the activities of superoxide dismutase and catalase and that those in the early stage did not relate directly to the above renal enzymatic systems.
为阐明头孢菌素（CER）诱导肾毒性的毒性和保护机制，主要研究了单次静脉注射剂量为100和1000mg/kg体重的CER的大鼠在15天内丙二醛肾生成以及黄嘌呤氧化酶、超氧化物歧化酶和过氧化氢酶肾活性的变化。在100mg/kg组中，所测定的上述指标保持在对照水平内。在1000mg/kg组中，观察到丙二醛的肾生成加速，分为以下两个阶段：早期（第3小时至第2天，尤其是第3小时）较高，后期（第2至第7天）更高。关于所测定的其他指标，在早期的12小时内，1000mg/kg组几乎未观察到显著差异变化，而在后期观察到黄嘌呤氧化酶肾活性升高以及超氧化物歧化酶和过氧化氢酶肾活性下降。这些结果表明，后期丙二醛生成的增加可能在酶学上由黄嘌呤氧化酶活性升高以及超氧化物歧化酶和过氧化氢酶活性下降共同解释，而早期的增加与上述肾酶系统无直接关系。
