Edaravone inhibits acute renal injury and cyst formation in cisplatin-treated rat kidney.
BACKGROUND
Although cis-diamminedichloroplatinum (II) (cisplatin) is an effective anticancer agent, its clinical use is highly limited predominantly due to its adverse effects on renal functions. The present work examined the therapeutic potential of edaravone, a free radical scavenger, for inhibiting cisplatin-induced renal injury.


METHODS
Edaravone, 3-methyl-1-phenyl-pyrazolin-5-one, was administrated intravenously at a dose of 30 mg/kg of body weight to male Wistar rats (200-220 g). After 30 min, cisplatin was injected intraperitoneally at a dose of 5 mg/kg of body weight. At the indicated times after the treatment, functions and histological changes of the kidney were analyzed. To test the therapeutic potential of edaravone in chemotherapy, its effect on the anticancer action of cisplatin was examined in ascites cancer-bearing rats.


RESULTS
We found that cisplatin rapidly impaired the respiratory function and DNA of mitochondria in renal proximal tubules, thereby inducing apoptosis of tubular epithelial cells within a few days and chronic renal dysfunction associated with multiple cysts one-year after the administration. Administration of edaravone inhibited the cisplatin-induced acute injury of mitochondria and their DNA and renal epithelial cell apoptosis as well as the occurrence of chronic renal dysfunction and multiple cyst formation. The anticancer effect of cisplatin remained unaffected by intravenous administrating of edaravone.


CONCLUSIONS
These results indicate that edaravone may have therapeutic potential for inhibiting the acute and chronic injury of the kidney induced by cisplatin.
Iguchi
Taro
T
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan.
Nishikawa
Manabu
M
Chang
Baojun
B
Muroya
Osuke
O
Sato
Eisuke F
EF
Nakatani
Tatsuya
T
Inoue
Masayasu
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals; D007668:Kidney / Q000293:injuries* / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D016166:Free Radical Scavengers; D005609:Free Radicals; D004247:DNA; D002945:Cisplatin; D000077553:Edaravone; D000983:Antipyrine