Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHII/eNOS/NO pathway
Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHII/eNOS/NO pathway
复制标题
槲皮素通过 ROS/ADMA/DDAHâ¡/eNOS/NO 途径保护血管内皮免受铁过载损伤
DOI：
10.1016/j.ejphar.2019.172885
复制
发表时间：
2020-02-05
影响因子：
5
通讯作者：
He, Ming
中科院分区：
文献类型：
--
作者：
Chen, Xuepiao;Li, Hongwei;He, Ming
The aberrant accumulation of iron causes vascular endothelium damage, which is thought to be associated with excess reactive oxygen species (ROS) generation. Quercetin (Que), as a flavonoid, has a certain ability to scavenge free radicals. Therefore, we aimed to explore the protective mechanism of Que on iron overload induced HUVECs injury focused on ROS/ADMA/DDAHII/eNOS/NO pathway. In this study, HUVECs was treated with 50 mu M iron dextran and 20 mu M Que for 48 h. We found that Que attenuated the damages induced by iron, as evidenced by decreased ROS generation, increased DDAHnexpression and activity, reduced ADMA level, increased NO content and p-eNOS/eNOS ratio, and eventually caused a decrease in apoptosis. After addition of pAD/DDAHII-shRNA, the effects of Que mentioned above were reversed. Meanwhile, iron overload induced mitochondrial oxidative stress, reduced mitochondrial membrane potential and increased mitochondrial permeability transition pores (mPTP) opening, which were also partially alleviated by Que. In addition, L-arginine (L-Arg), a ADMA competition substrate, ciclosporin A (CsA), a mPTP blocking agent, and edaravone (Eda), a free radical scavenger, were used as positive control reagents. The effects of Que were similar to that of L-Arg, CsA and Eda treatment. These results illustrated that Que could attenuate iron overload induced HUVECs mitochondrial dysfunction via ROS/ADMA/DDAHII/eNOS/NO pathway.
