The investigation of protective effect of Thymoquinone on cisplatin-induced nephrotoxicity

Cisplatin is a widely used an antineoplastic agent for the treatment of several solid tumors. The well-known complication of sisplatin administration is acute kidney injury even vigorous intravenous saline infusion. Acute kidney injury by sisplatin is multifactorial, including oxidative stress, inflammation and changes in cell cycle.Thymoquinone (TQ) had been shown to protect organs against oxidative damage induced by variety of freee radical generating agents. We investigated the protective effects of TQ against sisplatin-induced nephrotoxicity.Male Wistar rats (n= 28, 8 wk-old between 180-245 gr) were divided into four groups: (i) control rats, (ii) sisplatin (7 mg/kg, IP single dose), (iii) TQ (10 mg/kg, orally), (iv) sisplatin (7 mg/kg, IP single dose)+ TQ (10 mg/kg, orally). Cisplatin administration resulted in significant increase in serum urea nitrogen and creatinine (P<0.001). Serum urea nitrogen and creatinine levels were lower in rats treated with sisplatin+TQ compared with rats treated sisplatin alone (P<0.05). The renal tissue MDA and 8-iso-PGF2? levels showed a significant increase in sisplatin-treated rats compared the control rats (P<0.001). The expression of renal OKT1 and OKT2 was significantly higher in sisplatin+TQ group compared with sisplatin group (P<0.05). Cisplatin-induced renal histopathological changes were significantly improved with TQ.These results show that sisplatin produces oxidative stres and renal damage. In conclusion, our study show that TQ, which reduce oxidative stres and ameloriates the expression of OKT1 and OKT2, has significant potential as a therapeutic intervention for sisplatin-induced renal injury. Thus OKT2 spesific antagonists may prevent the nephrotoxicity of sisplatin.Keywords: cisplatin, thymoquinone (TQ), oxidative damage, organic cation transporter.