Artemisinin Alleviates Alcohol-Induced Cardiotoxicity by Inhibiting Ferroptosis via the Nrf2/NQO1 Pathway In Vivo and In Vitro.

Abstract

The present study was designed to explore the protective effects of artemisinin on alcohol-induced cardiac injuries and its mechanisms. In H9c2 cells, cell viability, reactive oxygen species (ROS), labile iron pool (LIP), and mitochondrial membrane potential (MMP) were measured. In the mouse model of alcohol-induced cardiomyopathy, body weight and electrocardiogram (ECG) were recorded every day. Heart tissue creatine kinase (CK), lactic dehydrogenase (LDH), iron, glutathione (GSH), malondialdehyde (MDA), and histological examination were measured. Western blot assay was performed to evaluate the expression of ferroptosis-related proteins in vitro and in vivo. The results in vitro showed that cell viability was increased, ROS and LIP contents were decreased, and the level of MMP was increased in artemisinin-treated H9c2 cells. Tissues CK, LDH, and GSH were improved after being treated with artemisinin. The ferroptosis biomarkers, including MDA and tissue iron, were attenuated after artemisinin treatment. Artemisinin protected the heart from alcohol damage by ECG and histological examination. Additionally, artemisinin down-regulated the expression of TfR and P53 and up-regulated Nrf2, HO-1, NQO1, and GPX4 expressions in vitro and in vivo. The results showed that both Fer-1 and artemisinin abolished ferroptosis. The data presented here showed that artemisinin had the potential to protect alcohol-induced cardiotoxicity through the inhibition of Nrf2/NQO1-dependent ferroptosis.