Prophylactic effect of diacerein against cisplatin-induced nephrotoxicity in rats

Background and Objective: Cisplatin is an effective chemotherapeutic agent for solid tumors, however its use is limited by nephrotoxicity. The current study investigated the effect of diacerein in cisplatin-induced nephrotoxicity in rats. Materials and Methods: Rats were randomly divided into 5 groups; control (untreated), diacerein control (100 mg kgG¹), cisplatin (5 mg kgG¹ i.p.), cisplatin+diacerein (50 mg kgG¹) and cisplatin+diacerein (100 mg kgG¹). Data were analyzed by one way ANOVA using GraphPad Prism. Results: Administration of cisplatin caused significant deterioration in renal function, designated by the increase in serum levels of both urea and creatinine, reduction in creatinine clearance, increase in microalbumin level and increase in fractionated sodium level. Cisplatin-induced renal injury was confirmed by histopathological finding in the form of damage of renal tubules. Cisplatin-induced renal damage was associated with significant increase in oxidative stress [increased renal contents of malondialdehyde (MDA), decreased reduced glutathione (GSH) and decreased activity of superoxide dismutase (SOD)] as well as by significant increase in the inflammatory mediator, tumor necrosis factor-α (TNF-α). Conclusion: Pretreatment with diacerein significantly ameliorated cisplatin-induced renal injury as evidenced both biochemically and histopathologically. The protective effect of diacerein was associated with amelioration of oxidative stress and reduction in TNF-α in renal tissue. Such data clarify that diacerein is a potential protective drug against cisplatin induced nephrotoxicity and its effect relies, at least partially, on its antioxidant and anti-inflammatory mechanisms.