Khurshid Faria, Iqbal Javeid, Ahmad Fiaz-Ud-Din, Lodhi Arslan Hussain, Malik Abdul, Akhtar Suhail, Khan Azmat Ali, Bux Marvi Imam, Younis Mohammed
Department of Pharmacology, Faculty of Pharmacy, University of Balochistan, Pakistan.
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan.
Heliyon. 2024 Apr 10;10(8):e29513. doi: 10.1016/j.heliyon.2024.e29513. eCollection 2024 Apr 30.
Hydrogen sulfide and possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats.
Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 μmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine and kidney samples were collected for biochemical assays and histopathological analysis.
Cisplatin decreased body weights and increased urinary output, while plasma creatinine and urea levels were elevated, but sodium and potassium concentrations were diminished. The renal function parameters, blood urea nitrogen and creatinine clearance, were raised and decreased respectively. Regarding markers of reactive oxygen species, plasma total superoxide dismutase was reduced, whereas malondiadehyde was augmented.Cisplatin also diminished plasma and urinary HS as well as plasma NO, while NaHS and L-arginine counteracted this activity on both redox-active molecules. Cisplatin cotreatment with NaHS, and/or L-arginine exhibited a reversal of all other measured parameters.
In current study, NaHS and L-arginine as monotherapy protected the rats from cisplatin-induced nephrotoxicity but the combination of both worked more effectively suggesting the augmented anti-inflammatory and antioxidative potential of test treatments when administered together.
硫化氢具有细胞保护活性，在体内，它们分别由外源性硫氢化钠和L-精氨酸产生。顺铂是一种用于治疗癌症的主要化疗药物，具有高发生率的肾毒性副作用。本研究旨在探讨硫氢化钠和L-精氨酸或其组合对顺铂诱导的大鼠肾毒性的影响。
给Wistar Kyoto大鼠单次腹腔注射顺铂（5mg/kg），随后每日给予硫氢化钠（56μmol/kg，腹腔注射）、L-精氨酸（饮用水中1.25g/L）或其组合，持续28天。收集死后的血浆、尿液和肾脏样本进行生化分析和组织病理学分析。
顺铂降低了体重并增加了尿量，同时血浆肌酐和尿素水平升高，但钠和钾浓度降低。肾功能参数血尿素氮和肌酐清除率分别升高和降低。关于活性氧标记物，血浆总超氧化物歧化酶降低，而丙二醛增加。顺铂还降低了血浆和尿液中的硫化氢以及血浆一氧化氮，而硫氢化钠和L-精氨酸抵消了对这两种氧化还原活性分子的这种作用。顺铂与硫氢化钠和/或L-精氨酸联合治疗使所有其他测量参数出现逆转。
在本研究中，硫氢化钠和L-精氨酸作为单一疗法可保护大鼠免受顺铂诱导的肾毒性，但两者联合使用效果更佳，表明联合给药时试验治疗的抗炎和抗氧化潜力增强。
