Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney.
BACKGROUND
Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of free radicals and has the antioxidant ability to inhibit lipid peroxidation. Its protective effect on brain ischemia has been shown. This study aimed to elucidate its possible therapeutic effects on renal oxidative stress in a rat ischemia/reperfusion model.


METHODS
Ischemic acute renal failure was induced by 45-minute clamp of the left renal artery followed by administration of edaravone. Renal function and pathologic findings were examined. The generation of free radicals was observed by the fluorogenic probe, dichlorodihydrofluorescein (CM-H(2)DCFDA), and lipid peroxidation was observed by immunochemical staining and Western analysis of 4-hydroxy-2-hexenal (HHE). The ability of edaravone to reduce in vitro oxidative stress was investigated using cultured human renal tubular cells (HKC-8) and the cell viability assay with Alamar blue.


RESULTS
Edaravone attenuated renal function and pathologic findings significantly. The protective effect of edaravone showed the dose-response was at the same level as that of dimethylthiourea. In addition, edaravone significantly reduced the generation of free radicals in the tubular cells indicated by CM-H(2)DCFDA. Immunochemical staining and Western analysis of HHE showed significant suppression of lipid peroxidation in edaravone-treated kidney. In HKC-8 cells loaded with CM-H(2)DCFDA, a marked elevation of fluorescence was observed after exposure to hydrogen peroxide (0.5 mmol/L, for 1 hour), which was reduced by edaravone. The cell viability assay with Alamar blue also showed the protective effect of edaravone.


CONCLUSIONS
Edaravone ameliorates renal ischemia/reperfusion injury by scavenging free radicals produced in renal tubular cells and inhibiting lipid peroxidation.
Doi
Kent
K
Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.
Suzuki
Yoshifumi
Y
Nakao
Akihide
A
Fujita
Toshiro
T
Noiri
Eisei
E
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine