Xanthorrhizol has a potential to attenuate the high dose cisplatin-induced nephrotoxicity in mice

Abstract

Cisplatin is a widely used anticancer drug, but it can produce undesirable side effects such as nephrotoxicity. The present study investigated the effect of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) on cisplatin-induced nephrotoxicity in mice. A single dose of cisplatin (45 mg/kg, i.p.) significantly elevated the levels of blood urea nitrogen, serum creatinine, and the kidney to body weight ratio, but the pretreatment of xanthorrhizol (200 mg/kg/day, per os) for 4 days significantly attenuated the cisplatin-induced nephrotoxicity. The preventive effect of xanthorrhizol was more efficacious than that of curcumin with the same amount (200 mg/kg). However, this effect seemed not to be related with the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors such as nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1). This is first time the preventive effect of xanthorrhizol on cisplatin-induced nephrotoxicity has been demonstrated, and these data suggest that the administration of xanthorrhizol is a promising approach in the treatment of nephrotoxicity caused by cisplatin.