Protective Effect of Silymarin on Cisplatin-induced Nephrotoxicity in Rats

Abstract

Cisplatin (CDDP) is a potent anticancer agents used for the treatment of solid tumors. However, its clinical use is often limited by its adverse effects including nephrotoxicity. The present study was designed to estimate if silymarin, a bioflavonoid with antioxidant potential can inhibit or at least ameliorate the alteration in some renal structures induced by cisplatin in rats or not. Five equal-sized groups (18 rats each) of male Sprague Dawley rats [Control, vehicle; cisplatin (5 mg/kg); silymarin (50 mg/kg) 2 h after cisplatin injection; and silymarin (50 mg/kg) 2 h before cisplatin injection] were used. Results revealed that cisplatin produced animal behavioral and morphological changes, as well as cellular and subcellular changes in kidneys. The most important changes were: decreased body weight, increased kidney wet weight, atrophied glomeruli, dilated urinary space, loss of PCT brush borders, hypertrophied podocyte pedicels, thickened glomerular basement membrane as well as tubular cell vacuolization. Post-treatment of silymarin 2 h after cisplatin however, significantly increase the body weight returning it to normal value, yet it failed in complete protection against the pathological alteration caused by cisplatin. Pre-treatment with silymarin 2 h before cisplatin significantly decreased the histological and ultrastructural changes induced by cisplatin and appear highly protective. These results suggested that the effects of cisplatin on glomerular and renal tubular cells morphology could be totally or to a great extent inhibited by silymarin.