The Renoprotective Effects of Liraglutide and Alfacalcidol against Cisplatin Induced Nephrotoxicity in Mice

Basma I. Fehil, Ahmed I. Yassin, Heba A. Mahmoud, Sabiha E. Hedya
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Abstract

Cisplatin (CP) is an important platinum-based chemotherapy agent widely used to treat solid tumors. However, nephrotoxicity is the main limiting adverse effect in 25%–35% of patients treated with even a single dose of CP. This study aimed to evaluate the role of liraglutide (LIRA) and alfacalcidol (ALFA), each of them alone and in combination, in prevention of CP-induced nephrotoxicity. Forty male albino mice were divided into five groups including normal control group and groups CP, CP with LIRA, CP with ALFA, or CP with LIRA and ALFA. Nephrotoxicity was induced by single intraperitoneal injection of CP in a dose 12mg/kg. LIRA and/or ALFA treatment was started 5 days before induction of nephrotoxicity and continued till the end of experiment. Kidney function tests, oxidative stress and ferroptosis parameters were assessed. Histopathological and immunohistochemical examination were performed on kidney tissues. Both LIRA and ALFA monotherapy resulted in a significant improvement in kidney function tests, increased antioxidant levels, inhibition of ferroptosis and improved histopathological findings. LIRA showed more improvement compared to ALFA and their combination showed better results than each one alone. In conclusion, LIRA and ALFA either alone or in combination, represent a promising preventive modality for amelioration of CP-induced nephrotoxicity.
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利拉鲁肽和阿法骨化醇对顺铂诱导的小鼠肾毒性的保护作用
顺铂(CP)是一种重要的铂类化疗药物,被广泛用于治疗实体瘤。然而,在接受过单剂顺铂治疗的患者中,25%-35%的患者会出现肾毒性这一主要的限制性不良反应。本研究旨在评估利拉鲁肽(LIRA)和阿法骨化醇(ALFA)各自单独或联合使用在预防氯化石蜡诱导的肾毒性方面的作用。将 40 只雄性白化小鼠分为 5 组,包括正常对照组、氯化石蜡组、氯化石蜡与 LIRA 组、氯化石蜡与 ALFA 组、氯化石蜡与 LIRA 和 ALFA 组。氯化石蜡单次腹腔注射剂量为 12 毫克/千克,诱导肾毒性。LIRA和/或ALFA治疗在肾毒性诱导前5天开始,并持续到实验结束。对肾功能测试、氧化应激和铁变态反应参数进行了评估。对肾组织进行组织病理学和免疫组化检查。LIRA和ALFA单药治疗均显著改善了肾功能测试、提高了抗氧化剂水平、抑制了铁蛋白沉积并改善了组织病理学结果。与 ALFA 相比,LIRA 的改善幅度更大,而两者联合使用的效果也比单独使用更好。总之,LIRA 和 ALFA 无论是单独使用还是联合使用,都是改善氯化石蜡诱发的肾毒性的一种很有前景的预防方法。
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