头孢噻啶、头孢噻吩和庆大霉素对雄性斯普拉格-道利大鼠肾皮质谷胱甘肽的消耗及肾毒性

Depletion of renal cortical glutathione and nephrotoxicity by cephaloridine, cephalothin and gentamicin in male Sprague-Dawley rats.

作者信息

Kuo C H, Hook J B

出版信息

Life Sci. 1982 Jul 19;31(3):255-60. doi: 10.1016/0024-3205(82)90586-0.

Abstract

Cephaloridine and gentamicin are selectively accumulated in renal cortex and produce necrosis or proximal tubular cells. However, the mechanisms responsible for renal cortical accumulation of these two antibiotics are quite different; therefore the early pathogenetic processes may not be the same. In the present study, effects of two cephalosporins (cephaloridine and cephalothin) and an aminoglycoside (gentamicin) on rat renal cortical glutathione were determined. Cephaloridine produced a dose-related depletion of renal cortical glutathione one hour following a single administration of the drug. In contrast, cephalothin in equivalent doses did not reduce renal cortical glutathione. Gentamicin had no effect on renal cortical glutathione, even when an acutely lethal dose (1000 mg/kg) was used. Pretreatment of rats with diethyl maleate (0.4 ml/kg) markedly depleted renal cortical glutathione and this pretreatment also potentiated cephaloridine nephrotoxicity. These results suggest that glutathione may play a protective role against cephaloridine but not gentamicin nephrotoxicity.

摘要

头孢噻啶和庆大霉素可选择性地蓄积于肾皮质，并导致坏死或近端肾小管细胞损伤。然而，这两种抗生素在肾皮质蓄积的机制却大不相同；因此，早期发病过程可能也不一样。在本研究中，测定了两种头孢菌素（头孢噻啶和头孢噻吩）及一种氨基糖苷类抗生素（庆大霉素）对大鼠肾皮质谷胱甘肽的影响。单次给药后1小时，头孢噻啶可使肾皮质谷胱甘肽呈剂量依赖性减少。相比之下，同等剂量的头孢噻吩并未降低肾皮质谷胱甘肽水平。即使使用急性致死剂量（1000mg/kg）的庆大霉素，其对肾皮质谷胱甘肽也没有影响。用马来酸二乙酯（0.4ml/kg）对大鼠进行预处理可显著消耗肾皮质谷胱甘肽，这种预处理还会增强头孢噻啶的肾毒性。这些结果表明，谷胱甘肽可能对头孢噻啶肾毒性具有保护作用，但对庆大霉素肾毒性则无此作用。