Tempol (4-hydroxy tempo) protects mice from cisplatin-induced acute kidney injury via modulation of expression of aquaporins and kidney injury molecule-1. (4th May 2022)

• Record Type: Journal Article
• Authors: Afjal, Mohd Amir; Goswami, Poonam; Ahmad, Shahzad; Dabeer, Sadaf; Akhter, Juheb; Salman, Mohd; Mangla, Anuradha; Raisuddin, Sheikh
• Is Part Of: Drug and chemical toxicology. Volume 45:Number 3(2022)
• Page Start: 1355
• Page End: 1363
• Publication Date: 2022-05-04
• Subjects: Anti-neoplastic drug -- acute kidney injury -- electrolyte imbalance -- nephric reabsorption -- nephroprotection; Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.1080/01480545.2020.1831011
• Languages: English
• ISSNs: 0148-0545

Abstract

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.