Cisplatin-Induced Nephrotoxicity in Rats: Modulatory Role of Simvastatin and Rosuvastatin against Apoptosis and Inflammation

Cisplatin use as a chemotherapeutic agent is restricted due to its nephrotoxicity. The current study investigates the possible mechanisms responsible for the nephro-protective effects of simvastatin (SIM) and rosuvastatin (RST) in cisplatin-induced nephrotoxicity in rats. Acute nephrotoxicity was induced in rats by single injection of cisplatin on the 10th day of the treatment period. Two groups received SIM and RST daily respectively, for 10 days prior to cisplatin injection. 5 days post cisplatin injection, blood samples were taken, rats were scarified and renal tissues were isolated for biochemical, immunohistochemical and histopathological assessments. Results of the study revealed that cisplatin-injected rats showed a reduction in the relative kidney weight with an elevation in the serum kidney function and renal inflammatory mediators viz. myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and interlukin-1β (IL-1β). Kidneys isolated from rats injected with cisplatin showed overexpression of apoptotic markers and a decrease in the expression of the anti-apototic markers. SIM and RST significantly improved relative kidney weight, serum kidney function and restored renal tissue concentrations of inflammatory mediators. Decreased renal expression of caspases-3, Bax with increased Bcl-2 expression and improved histopathological pictures of treatment groups were observed. Our results suggest that SIM and RST have nephroprotective properties against cisplatin-induced nephrotoxicity due to their anti-inflammatory and anti-apoptotic effects.