Alamandine通过靶向氧化应激和炎症减轻甲氨蝶呤诱导的大鼠肾毒性

A. Yıldız, M. Aras, M. Gunata, M. Durhan, S. Polat, H. Parlakpınar, Y. Cigremis, N. Vardı
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摘要

目的:甲氨蝶呤(Mtx)引起的肾毒性是化疗中最重要的问题之一。氧化应激和炎症是甲氨蝶呤引起肾毒性的主要病理机制。Alamandine (Ala)是肾素-血管紧张素系统(RAS)的新成员,是一种具有抗氧化和抗炎功能的重要肽。本研究探讨Ala是否通过降低氧化应激和炎症来改善mtx诱导的肾损伤。材料与方法:雄性Wistar白化大鼠分为对照组、Mtx组、Mtx+Ala组。在实验结束时,肾脏组织被迅速移除。通过测定谷胱甘肽(GSH)和丙二醛(MDA)水平来确定肾组织中的氧化状态。此外,对组织样本进行组织病理学和免疫组化检测,检测热休克蛋白60 (HSP60)、caspase-3、肿瘤坏死因子-α (TNF-α)和受体相互作用蛋白激酶3 (RIPK3)。结果:Mtx治疗导致GSH含量降低,MDA水平升高,热休克蛋白60 (HSP60)和caspase-3表达升高。甲氨蝶呤处理大鼠肾脏组织的这些变化引发以细胞凋亡和肾损伤为特征的氧化应激。Mtx还显著增加炎症标志物TNF-α和坏死下垂标志物RIPK3的表达。然而,Ala通过抑制氧化应激和炎症,减少细胞凋亡和坏死下垂,显著减轻mtx诱导的肾损伤。结论:综上所述,我们的研究结果支持Ala治疗可以作为一种新的有前途的治疗策略来治疗甲氨蝶呤引起的肾毒性。关键词:Alamandine;甲氨蝶呤;氧化应激;炎症;细胞凋亡;necroptosis;肾毒性
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alamandine alleviates methotrexate-induced nephrotoxicity in rats by targeting oxidative stress and inflammation
Aim: Nephrotoxicity due to the use of methotrexate (Mtx) is one of the most important problems associated with chemotherapy. Oxidative stress and inflammation are the major pathomechanisms of Mtx-induced nephrotoxicity. Alamandine (Ala), a new member of the renin-angiotensin system (RAS), is an important peptide with antioxidant and anti-inflammatory capacities. In this study, it was investigated whether Ala ameliorates Mtx-induced kidney damage by reducing oxidative stress and inflammation. Materials and Methods: Male Wistar albino rats were assigned into three groups: control group, Mtx group, and Mtx+Ala group. At the end of the experiment, kidney tissues were quickly removed. Glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative state in kidney tissues. In addition, tissue samples were assessed as histopathological and immunohistochemical for heat shock protein 60 (HSP60), caspase-3, tumor necrosis factor-α (TNF-α), and receptor-interacting protein kinase-3 (RIPK3). Results: Mtx treatment resulted in reduced GSH content, elevated MDA level, increased heat shock protein 60 (HSP60), and caspase-3 expression. These changes in kidney tissues of rats treated with Mtx triggered oxidative stress characterized by apoptosis and kidney damage. Mtx also markedly increased the expression of TNF-α, an inflammation marker, and RIPK3, a marker of necroptosis. However, Ala administration significantly alleviated Mtx-induced kidney damage by reducing apoptosis and necroptosis by suppressing oxidative stress and inflammation. Conclusion: Taken together, our results support that Ala treatment can serve as a new and promising therapeutic strategy against Mtx-induced nephrotoxicity. Keywords: Alamandine; methotrexate; oxidative stress; inflammation; apoptosis; necroptosis; nephrotoxicity
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