Quercetin Protects H9c2 Cardiomyocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Oxidative Stress and Mitochondrial Apoptosis by Regulating the ERK1/2/DRP1 Signaling Pathway.

Fen Li,Dongsheng Li,Jie Yan,Haifeng Chen,Shifan Tang,Xisheng Yan,Jianguang Liu,Chian-Jiun Liou

doi:10.1155/2021/7522175

Abstract

Reperfusion of blood flow during ischemic myocardium resuscitation induces ischemia/reperfusion (I/R) injury. Oxidative stress has been identified as a major cause in this process. Quercetin (QCT) is a member of the flavonoid family that exerts antioxidant effects. The aim of this study was to investigate the preventive effects of QCT on I/R injury and its underlying mechanism. To this end, H9c2 cardiomyocytes were treated with different concentrations of QCT (10, 20, and 40 μM) and subsequently subjected to oxygen-glucose deprivation/reperfusion (OGD/R) administration. The results indicated that OGD/R-induced oxidative stress, apoptosis, and mitochondrial dysfunction in H9c2 cardiomyocytes were aggravated following 40 μM QCT treatment and alleviated following the administration of 10 and 20 μM QCT prior to OGD/R treatment. In addition, OGD/R treatment inactivated ERK1/2 signaling activation. The effect was mitigated using 10 and 20 μM QCT prior to OGD/R treatment. In conclusion, these results suggested that low concentrations of QCT might alleviate I/R injury by suppressing oxidative stress and improving mitochondrial function through the regulation of ERK1/2-DRP1 signaling, providing a potential candidate for I/R injury prevention.

Highlights

Cardiovascular diseases are the primary cause of human mortality worldwide, leading to more than 17 million deaths annually and accounting for 31% of global mortality [1, 2]
Low Concentrations of QCT Promoted Proliferation and Inhibited Oxidative Stress Response in oxygen-glucose deprivation/reperfusion (OGD/R)-Induced H9c2 Cells. e Cell Counting Kit-8 (CCK-8) assay showed that OGD/R treatment inhibited the proliferation of H9c2 cells
QCT concentrations of 10, 20, and 40 μM were chosen for subsequent experiments to investigate the specific effects of QCT on OGD/R-induced damage. e results indicated that OGD/R treatment decreased the proliferation (Figure 1(b)), SOD (Figure 1(d)), and eNOS (Figure 1(e)) levels and increased the MDA level (Figure 1(c)) and the proportion of cells with increased reactive oxygen species (ROS) (Figure 1(f)). e effects of OGD/R were aggravated with 40 μM QCT treatment and mitigated with 10 and 20 μM QCT and NAC treatment prior to OGD/R treatment

Summary

Introduction

Cardiovascular diseases are the primary cause of human mortality worldwide, leading to more than 17 million deaths annually and accounting for 31% of global mortality [1, 2]. Excessive ROS generation leads to the opening of the mitochondrial permeability transition pore, lipid peroxidation, and DNA damage, thereby causing apoptosis [10, 11]. Us, strategies that prevent or alleviate oxidative stress response and cardiomyocyte apoptosis are advisable for the treatment of myocardial I/R damage. QCT alleviated DOX-induced toxicity in cardiomyocytes by promoting mitochondrial function and attenuating oxidative stress [18]. The preventive effect of QCT against myocardial I/R damage and its underlying mechanisms needs to be elucidated Based on these findings, we hypothesized that QCT can act as a candidate for myocardial I/R damage prevention, and its mechanism may be associated with oxidative stress and mitochondrial function modulation.

Materials and Methods

Results

Discussion

Conclusion

Conflicts of Interest