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Purpose: To investigate the possible protective role of curcumin and α-tocopherol against cisplatininduced nephrotoxicity in rat.Methods: Male Wistar rats were divided into five groups. Groups 1 and 2 were intraperitoneally (i.p.) injected with normal saline and cisplatin (20 mg/kg), respectively. Groups 3, 4 and 5 were pre-treated with a single doses of α-tocopherol (250 mg/kg), curcumin (200 mg/kg) and α-tocopherol with curcumin, respectively, for 24 h prior to the administration of cisplatin. After 72 h following injection, specimens were collected. Serum blood urea nitrogen (BUN), creatinine and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase activities, kidney histopathological study and gene expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and p38 mitogenactivated protein kinase (p38-MAPK) were investigated.Results: Pre-treatment with combined curcumin and α-tocopherol exhibited significantly reduced MDA levels and enhanced activities of SOD and catalase compared with cisplatin-treated group (p < 0.05). It also improved BUN as well as creatinine levels and kidney histopathology. Moreover, gene expressions of NADPH oxidase were decreased, whereas p38-MAPK gene expressions were not significant compared with cisplatin-treated group.Conclusion: Combined curcumin and α-tocopherol are able to reduce cisplatin-induced nephrotoxicity via possible inhibition of NADPH oxidase, resulting in improvement of kidney function and histology.Keywords: Cisplatin, Oxidative stress, Curcumin, α-Tocopherol, Nephrotoxicity.