Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Molecular Neurobiology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Drug Chem Toxicol. 2022 May;45(3):1355-1363. doi: 10.1080/01480545.2020.1831011. Epub 2020 Oct 20.
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, ) pretreatment with CP (20 mg/kg ) 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.
替普瑞酮(4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基)是一种多效抗氧化剂,据报道可预防顺铂(CP)诱导的肾毒性。然而,替普瑞酮在改善 CP 诱导的肾毒性中肾功能的作用机制尚不完全清楚。我们研究了替普瑞酮对 CP 诱导的肾损伤分子-1(KIM-1)和水通道蛋白(AQP)改变的抑制作用。CP(20mg/kg)处理前用替普瑞酮(100mg/kg)预处理,可恢复肾功能标志物,包括电解质。CP 处理上调了 KIM-1 的 mRNA 表达,下调了 AQP 和精氨酸加压素(AVP)的表达,而替普瑞酮则减弱了这种表达。免疫印迹分析显示 CP 诱导的 KIM-1 和 AQP 表达的改变被替普瑞酮恢复。免疫荧光研究还显示替普瑞酮对 CP 处理小鼠 AQP2 表达的恢复作用。总之,本研究提供了实验证据,表明替普瑞酮通过恢复 AQP、AVP 和 KIM-1 水平来解决尿液浓缩缺陷,这表明替普瑞酮在改善接受 CP 治疗的癌症患者的急性肾损伤方面具有潜在用途。