Quercetin protects the vascular endothelium against iron overload damages. - GreenMedInfo Summary
Quercetin protects the vascular endothelium against iron overload damages via ROS/ADMA/DDAHⅡ/eNOS/NO pathway.
Eur J Pharmacol. 2020 Feb 5 ;868:172885. Epub 2019 Dec 20. PMID: 31870832
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 μM iron dextran and 20 μM Que for 48 h. We found that Que attenuated the damages induced by iron, as evidenced by decreased ROS generation, increased DDAHⅡexpression 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.