Effects of curcumin on anion/cation transporters and multidrug response proteins in cisplatin induced nephrotoxicity

Abstract

Nephrotoxicity is the major side effect that restricts cisplatin usage in solid tumor therapy and oxidative stress has a prominent role in the pathophysiology of cisplatin nephrotoxicity. Curcumin is an effective antioxidant on oxygen metabolites. Organic anion and cation proteins (OATs, OCTs) serve for the transport of the chemicals into kidney cells and excretion to the urine of these molecules become via multi drug resistance associated proteins (MRPs). We investigated the effects of curcumin on OATs, OCTs and MRPs in rats with cisplatin induced nephrotoxicity. Wistar albino rats (6 weeks old, n=28) were assigned to four groups as; (i): control; (ii): curcumin (100 mg/kg/ day); (iii): cisplatin (7 mg/kg-single dose, i. p); (iv): curcumin + cisplatin (100 mg/kg/day + 7 mg/kg-single dose, i. p). Nephrotoxicity was associated with elevations in serum urea and creatinine concentrations and oxidative stress as reflected by elevated renal malondialdehyde (MDA). Rat kidney with cisplatin induced nephrotoxicity had decreased the OAT-1, OAT-3, OCT-1 and OCT-2 levels and increased MRP2 and MRP4 levels as compared to healthy rat kidneys. However, administration of resveratrol (100 mg/kg/day) partially alleviated the cisplatin-induced nephrotoxicity as reflected suppressed the expression oxidative stress parameters and OATs and OCTs levels and enhanced the MRPs levels in the kidney of cisplatin treated rats. Furthermore, the histopathological changes due to cisplatin were ameliorated by curcumin treatment. In conclusion, curcumin has the potential of preventing the cisplatin induced nephrotoxicity via the modulation OATs, OCTs and MRPs expressions in the kidney.