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

Mohd Amir Afjal, Poonam Goswami, Shahzad Ahmad, Sadaf Dabeer, Juheb Akhter, Mohd Salman, Anuradha Mangla, Sheikh Raisuddin

Drug and chemical toxicology 2022 May

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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.

Citation

Mohd Amir Afjal, Poonam Goswami, Shahzad Ahmad, Sadaf Dabeer, Juheb Akhter, Mohd Salman, Anuradha Mangla, Sheikh Raisuddin. Tempol (4-hydroxy tempo) protects mice from cisplatin-induced acute kidney injury via modulation of expression of aquaporins and kidney injury molecule-1. Drug and chemical toxicology. 2022 May;45(3):1355-1363