Tempol (4-hydroxy tempo) protects mice from cisplatin-induced acute kidney injury <i>via</i> modulation of expression of aquaporins and kidney injury molecule-1

Abstract

Tempol (4-hydroxy tempo), a pleiotropic antioxidant is reported to afford protection against cisplatin (CP)-induced nephrotoxicity. However, molecular mechanisms of action of tempol in improving the renal function in CP-induced nephrotoxicity are not fully understood. We investigated the attenuating effect of tempol against CP-induced alterations in kidney injury molecule-1 (KIM-1) and aquaporins (AQPs) in mice. Tempol (100 mg/kg, po) pretreatment with CP (20 mg/kg ip) showed restoration in renal function markers including electrolytes. CP treatment upregulated mRNA expression of KIM-1 and downregulated AQP and arginine vasopressin (AVP) expression which was attenuated by tempol. Immunoblotting analysis revealed that CP-induced alterations in KIM-1 and AQP expression were restored by tempol. Immunofluorocense study also showed restorative effect of tempol on the expression of AQP2 in CP-treated mice. In conclusion, this study provides experimental evidence that tempol resolved urinary concentration defect by the restoration of AQP, AVP and KIM-1 levels indicating a potential use of tempol in ameliorating the AKI in cancer patients under the treatment with CP.