二硫苏糖醇对大鼠肾皮质切片顺铂毒性的体外改善作用。

Amelioration of cisplatin toxicity in rat renal cortical slices by dithiothreitol in vitro.

Zhang J G, Zhong L F, Zhang M, Ma X L, Xia Y X, Lindup W E

Department of Toxicology, Dalian Medical College, People's Republic of China.

Hum Exp Toxicol. 1994 Feb;13(2):89-93. doi: 10.1177/096032719401300205.

Abstract

The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2. The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondialdehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3. Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol l-1) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4. The results suggest that the protective mechanism of DTT is its antioxidative action. DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.

摘要

用大鼠肾皮质切片研究了二硫苏糖醇（DTT）对顺铂诱导的肾毒性的保护作用。2. 顺铂（2 mmol l-1）的肾毒性作用表现为多种方式：Na+和水含量增加，而K+减少。切片中丙二醛（MDA）浓度和释放到培养基中的乳酸脱氢酶（LDH）增加。切片中对氨基马尿酸（PAH）的摄取、葡萄糖的合成以及谷胱甘肽（GSH）浓度均降低。3. 尽管切片对铂（Pt）的摄取因DTT而增加，但DTT（0.5 - 2 mmol l-1）以浓度相关的方式改善了顺铂的所有这些毒性作用。4. 结果表明，DTT的保护机制是其抗氧化作用。然而，DTT也是一种金属螯合剂，因此不能排除DTT通过螯合Pt产生保护作用的可能性。