Therapeutic potential of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion injury-induced acute renal failure in rats

Abstract

This study was designed to investigate the role of 7,8-dimethoxycoumarin on cisplatin- and ischemia/reperfusion (I/R)-induced acute renal failure in rats. Acute renal failure was induced in rats by administration of a single dose of cisplatin (CP) (6 mg/kg, intraperitoneally on day 6) and occlusion of the left renal artery for 45 min (I) and opened for the next 24 h (R). The drug samples of 7,8-dimethoxycoumarin (DMC, 50, 75, and 100 mg/kg) and cyclosporin A (50 μM/kg) were administered orally for six consecutive days. Administration of a single dose of cisplatin and I/R event has significantly raised blood urea nitrogen and creatinine, N-acetyl beta-D: -glucosaminidase, and thiobarbituric acid reactive substances but decreased FrNa, creatinine clearance, reduced glutathione (GSH), mitochondrial cytochrome c oxidase, and adenosine triphosphate levels. Further, pretreatment of DMC (50, 75, and 100 mg/kg, p.o., for six consecutive days) has ameliorated the CP- and I/R-induced biochemical and histopathological changes in a dose-dependent manner. Furthermore, 75 and 100 mg/kg of 7,8-dimethoxycoumarin has shown to possess the significant renoprotective effect similar to that of the cyclosporin A-treated group which served as positive control. Based on the results of the present study, it has been concluded that 7,8-dimethoxycoumarin protects the kidney against the CP and I/R injury via antioxidant, anti-inflammatory, and inactivation of mitochondrial permeability transition pore opening.