Chemopreventive effect of tadalafil in cisplatin-induced nephrotoxicity in rats

[摘要] Summary: Nephrotoxicity remains a common untoward effect of cisplatin therapy with limited effective chemopreventive options available till date. This study aims to evaluate the possible chemopreventive effect and mechanism(s) of action of 2 mgkg -1and 5 mgkg -1of Tadalafil in cisplatin-induced nephrotoxic rats. In this study, twenty-five male Wistar rats were randomly divided into five groups ( n= 5 rats per group) and daily pretreated with oral doses of distilled water (10 mLkg -1 ), ascorbic acid (100 mgkg -1 ), Tadalafil (2 mgkg -1and 5 mgkg -1 ) for 7 days before cisplatin (5 mgkg -1 , intraperitoneal) was administered. 72 hours post-cisplatin injections, rats were sacrificed humanely and blood samples for serum electrolytes, urea and creatinine and renal tissues for reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malonialdehyde dehydrogenase (MAD) assays and histopathology were collected. Results showed that cisplatin injection caused significant decreases in the serum sodium (Na + ), potassium (K + ), bicarbonate (HCO 3- ), calcium (Ca 2+ ), phosphate (PO 42- ) and concomitant significant increases in the serum urea and creatinine levels. In addition, there were significant decreases in the renal tissue GSH, SOD, CAT and increased MAD and GSH-Px levels which were corroborated by histopathological features of tubulonephritis. However, these histo-biochemical alterations were significantly attenuated by ascorbic acid and Tadalafil pretreatments. Overall, results of this study showed the chemopreventive potential of Tadalafil against cisplatin-induced nephrotoxicity which was possibly mediated via antioxidant and anti-lipoperoxidation mechanisms. Keywords:Cisplatin-induced nephrotoxicity, Renal function parameters, Oxidative markers, Histopathology

[学科分类] 内科医学

[关键词] Cisplatin-induced nephrotoxicity;Renal function parameters;Oxidative markers;Histopathology