Pitavastatin attenuates cisplatin-induced renal injury by targeting MAPK and apoptotic pathways

Abstract

Objective: Anti-neoplastic drug cisplatin is prescribed widely for treatment of a variety of malignancies. Its use has been restricted lately due to severe renal toxicity. The purpose of current study was to investigate the effect of pitavastatin (a hypolipidaemic drug) in cisplatin-induced acute kidney injury in rats. Method: Male Wistar rats (150–200 g) were treated with different doses of pitavastatin (0.16, 0.32 and 0.64 mg/kg per day p.o.; 10 days). On 7th day of the study, rats were administered cisplatin (8 mg/kg i.p.). Rats were euthanized (11th day), and blood and tissues were processed to evaluate biochemical, histopathological and ultrastructural parameters along with the analysis of immunohistochemistry and DNA-fragmentation studies. Protein expressions were analysed to demonstrate the underlying molecular mechanisms. Key findings: In the study group with cisplatin insult, KFT parameters were found to be elevated, concentration of apoptotic markers was found to be increased, histopathological and ultramicroscopical architecture was found to be distorted and the expression of MAPK proteins was also found to be elevated as compared to the normal group rats. Pitavastatin treatment alleviated all these anomalies. Conclusion: Cisplatin-induced acute renal injury was improved on administration of pitavastatin via inhibition of MAPK and apoptotic pathway.