Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats.
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.
Sueishi
Kunihiko
K
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Mishima
Kazuto
K
Makino
Kazutaka
K
Itoh
Yoshinori
Y
Tsuruya
Kazuhiko
K
Hirakata
Hideki
H
Oishi
Ryozo
R
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin; D000077553:Edaravone; D000983:Antipyrine