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表没食子儿茶素没食子酸酯(EGCG)通过调节代谢平衡和涉及 Drp1 介导线粒体分裂的线粒体动力学减轻小鼠的肾损伤。

Polyphenol (-)-Epigallocatechin Gallate (EGCG) mitigated kidney injury by regulating metabolic homeostasis and mitochondrial dynamics involvement with Drp1-mediated mitochondrial fission in mice.

机构信息

State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, 330047, China.

Jinchan Pi, College of Future Technology, Nanchang University, Nanchang, 330031, China.

出版信息

Food Chem Toxicol. 2024 Sep;191:114906. doi: 10.1016/j.fct.2024.114906. Epub 2024 Jul 31.

Abstract

The study aimed to examine effects of (-)-epigallocatechin-3-gallate (EGCG) on energy metabolism and mitochondrial dynamics in mouse model of renal injury caused by doxorubicin (DOX). Here, mice were divided into Control group, EGCG-only treated group, DOX group, and three doses of EGCG plus DOX groups. Our results showed that EGCG behaved beneficial effects against kidney injury via attenuation of pathological changes in kidney tissue, which was confirmed by reducing serum creatinine (SCr), blood urea nitrogen (BUN), and apoptosis. Subsequently, changes in reactive oxygen species generation, malondialdehyde content, and activities of antioxidant enzymes were considerably ameliorated in EGCG + DOX groups when compared to DOX group. Furthermore, EGCG-evoked renal protection was associated with increases of mitochondrial membrane potential and decreases of mitochondrial fission protein Dynamin-related protein 1 (Drp1). Moreover, changing glycolysis into mitochondrial oxidative phosphorylation was observed, evidenced by controlling activities of malate dehydrogenase (MDH) and hexokinase (HK) in EGCG + DOX groups when compared to DOX group, indicating that reprogramming energy metabolism was linked to EGCG-induced renal protection in mice. Therefore, EGCG was demonstrated to have a protective effect against kidney injury by reducing oxidative damage, metabolic disorders, and mitochondrial dysfunction, suggesting that EGCG has potential as a feasible strategy to prevent kidney injury.

摘要

本研究旨在探讨表没食子儿茶素没食子酸酯(EGCG)对阿霉素(DOX)诱导的肾损伤小鼠模型能量代谢和线粒体动力学的影响。在这里,将小鼠分为对照组、仅 EGCG 处理组、DOX 组和 3 种剂量 EGCG+DOX 组。我们的结果表明,EGCG 通过减轻肾组织的病理变化对肾损伤表现出有益的作用,这一点通过降低血清肌酐(SCr)、血尿素氮(BUN)和细胞凋亡得到了证实。随后,与 DOX 组相比,EGCG+DOX 组中活性氧生成、丙二醛含量和抗氧化酶活性的变化得到了显著改善。此外,EGCG 诱导的肾脏保护与线粒体膜电位的增加和分裂蛋白 Dynamin-related protein 1(Drp1)的减少有关。此外,还观察到糖酵解向线粒体氧化磷酸化的转变,这一点在 EGCG+DOX 组中通过控制苹果酸脱氢酶(MDH)和己糖激酶(HK)的活性与 DOX 组相比得到了证实,表明能量代谢的重编程与 EGCG 诱导的小鼠肾脏保护有关。因此,EGCG 通过减少氧化损伤、代谢紊乱和线粒体功能障碍显示出对肾损伤的保护作用,这表明 EGCG 作为一种预防肾损伤的可行策略具有潜力。

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