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Protective effect of rutin against carbon tetrachloride-induced oxidative stress, inflammation and apoptosis in mouse kidney associated with the ceramide, MAPKs, p53 and calpain activities
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-03-06 , DOI: 10.1016/j.cbi.2018.03.003
Jie-Qiong Ma , Chan-Min Liu , Wei Yang

Rutin, a natural flavonoid, possess beneficial health effects. However, its renoprotective effect against carbon tetrachloride (CCl4) induced injury and the underlying mechanism is not clarified. The current study aims is to identify the therapeutic effects of rutin on oxidative stress, inflammation and apoptosis in mouse kidney exposed to CCl4. ICR mice received CCl4 with or without rutin co-administration for one week. Compared with the control group, mice receiving CCl4 alone showed kidney injury as evidenced by elevation in serum biochemical markers, inflammation, caspase-3 activity and apoptosis in kidney, while rutin administration significantly attenuated these pathophysiological changes. Exploration of the underlying mechanisms of its action demonstrated that rutin reduced the ROS, calpain and ceramide levels in mouse kidneys. Rutin significantly decreased the p53, TNF-α, IL-1β activities and mitogen-activated protein kinase (MAPK) phosphorylation in the kidneys. In addition, rutin increased the levels of Bcl-2 protein and reduced levels protein of Bax. Rutin also inhibited the release of cytochrome C from mitochondria in kidneys of the CCl4-treated mice. Taken together, rutin ameliorates CCl4-induced oxidative stress, inflammation and apoptosis through regulating the ceramide, MAPK, p53 and calpain activities and thereby suppressing apoptosis by the mitochondrial pathway.



中文翻译:

芦丁对神经酰胺,MAPK,p53和钙蛋白酶活性相关的四氯化碳诱导的小鼠肾脏氧化应激,炎症和细胞凋亡的保护作用

天然黄酮类芦丁具有有益健康的功效。但是,其对四氯化碳(CCl 4)诱导的损伤的肾保护作用及其潜在机理尚不清楚。当前的研究目的是鉴定芦丁对暴露于CCl 4的小鼠肾脏的氧化应激,炎症和细胞凋亡的治疗作用。ICR小鼠接受CCl 4联合或不联合芦丁联合治疗一周。与对照组相比,接受CCl 4的小鼠血清生化标志物的升高,炎症,caspase-3活性和肾细胞凋亡证明了单独使用肾损伤,而芦丁的给药则显着减轻了这些病理生理变化。探索其作用的潜在机制表明,芦丁可降低小鼠肾脏中的ROS,钙蛋白酶和神经酰胺水平。芦丁显着降低了肾脏中的p53,TNF-α,IL-1β活性和有丝分裂原激活的蛋白激酶(MAPK)磷酸化。此外,芦丁增加了Bcl-2蛋白的水平,降低了Bax蛋白的水平。芦丁还抑制了CCl 4处理小鼠肾脏中线粒体中细胞色素C的释放。芦丁合在一起可改善CCl 4通过调节神经酰胺,MAPK,p53和钙蛋白酶活性来诱导氧化应激,炎症和细胞凋亡,从而通过线粒体途径抑制细胞凋亡。

更新日期:2018-03-06
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