Journal
DRUG AND CHEMICAL TOXICOLOGY
Volume 45, Issue 3, Pages 1355-1363Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/01480545.2020.1831011
Keywords
Anti-neoplastic drug; acute kidney injury; electrolyte imbalance; nephric reabsorption; nephroprotection
Funding
- Senior Research Fellowship of UGC-BSR [F. 25-1/2013-14(BSR)/7-91/2007(BSR)]
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Tempol has been found to ameliorate cisplatin-induced nephrotoxicity and restore the levels of renal function markers. Additionally, it can attenuate the effects of cisplatin on genes and proteins related to kidney injury.
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/kgip) 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.
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