Vitamin C dose-dependently ameliorates renal hemodynamic toxicity of cisplatin in adult Swiss albino rats: a histopathologic and biochemical study

Abstract

Nephrotoxicity is usually thought of as a common invariable consequence of hemodynamic toxicity whose effects, including oliguria and dysuria, has largely limited the clinical use of cisplatin. In this study, we investigated the protective effects of low and high dose of vitamin C against cisplatin-induced rat nephrotoxicity. Hence, 50 adult male Swiss albino rats were randomly divided into five equal groups to receive a corresponding dose of either normal saline as control, vitamin C (600 mg/kg/BW, i.v.), or cisplatin alone (7 mg/kg/BW, i.p.) or in combination with vitamin C at low dose (200 mg/kg/BW, i.v.) and high dose (600 mg/kg/BW, i.v.) for 9 days. Daily administration of cisplatin at a dose of 7 mg/kg/BW resulted in a significant increase in oxidative stress in renal tissues and plasma and a concomitant decrease in the creatinine clearance and renal blood flow as a result of early hemodynamic toxicity. Histopathological examination revealed acute tubular necrosis with hyaline cast formation triggered by cisplatin over 9 days of experiment. Further biochemical studies showed protecting effects of supplemented vitamin C at a high dose, illustrated by slowdown in the urinary enzyme activity, a significant decrease in plasma lipid peroxidation, and an increased tissue superoxide dismutase activity with recovery in the glomerular hemodynamicity and the ATPase activity up to 50 % when compared to controls and rats receiving low-dose. In high-dose animals, normal glomerular and tubular function on recovery from toxic renal failure led us to conclude that antioxidant property of vitamin C increases with dose, and, therefore, high dose of vitamin C prevents both functional and histological renal changes induced by cisplatin in rats, more efficient than low dose of the vitamin.