Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats
Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats
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DOI：
10.1016/s0014-2999(02)02251-3
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发表时间：
2002-09-13
影响因子：
5
通讯作者：
Oishi, R
中科院分区：
文献类型：
--
作者：
Sueishi, K;Mishima, K;Oishi, R
急性肾功能衰竭是顺铂化疗的剂量限制因素。在这里，我们显示了依达拉奉，一种最近开发的临床使用的自由基清除剂，对顺铂诱导的大鼠肾功能不全的保护作用。注射顺铂（5-10 mg/kg）后第4天，大鼠血清尿素氮和肌酐明显升高，近端肾小管出现空泡化、坏死和蛋白管型等组织学改变。依达拉奉（1-10 mg/kg，i. v.，2次/d，共3 d）可逆转顺铂引起的血尿素氮和肌酐升高，并呈剂量依赖性。特别是，依达拉奉的保护作用在10 mg/kg时几乎完全。此外，该化合物仍然是完全有效的，当它只在顺铂注射后的第二天给药。另一方面，肾组织中谷胱甘肽含量在顺铂注射后第4天降低，这被依达拉奉后期治疗逆转。这些结果表明，临床上可用的自由基清除剂依达拉奉是潜在的有用的预防顺铂诱导的肾毒性。(C)2002 Elsevier Science B. V.保留所有权利。
Acute renal failure is a dose-limiting factor of cisplatin chemotherapy. Here, we show the protective effect of edaravone, a recently developed radical scavenger for clinical use, against cisplatin-induced renal dysfunction in rats. A marked increase in blood urea nitrogen and creatinine in serum, and histological changes including vacuolation, necrosis and protein casts were observed in proximal renal tubules at the fourth day after cisplatin injection (5-10 mg/kg). Repeated injection of edaravone (1-10 mg/kg, i.v. twice a day for 3 days) reversed the cisplatin-induced elevation of blood urea nitrogen and creatinine, and morphological changes in a dose-dependent manner. In particular, the protective effect of edaravone was almost complete at 10 mg/kg. Moreover, the compound was still fully effective, when it was administered only at the second day after cisplatin injection. On the other hand, the glutathione content in renal tissues lowered at the fourth day after cisplatin injection, which was reversed by the late treatment with edaravone. These findings suggest that the clinically available radical scavenger edaravone is potentially useful for the prevention of cisplatin-induced renal toxicity. (C) 2002 Elsevier Science B.V. All rights reserved.