Ferroptosis-Specific Inhibitor Ferrostatin-1 Relieves H(2)O(2)-Induced Redox Imbalance in Primary Cardiomyocytes through the Nrf2/ARE Pathway

OBJECTIVE: Ischemic heart disease (IHD) has always been the focus of attention of many researchers in cardiovascular disease, and its pathogenesis is also very complicated. Ferroptosis may be involved in the occurrence and development of IHD. METHODS: First, primary cardiomyocytes were treated with H(2)O(2) to simulate the IHD in vitro model. After pretreatment with different concentrations of ferrostatin-1, cell survival rate was detected by MTT method, cell apoptosis was detected by TUNEL staining and flow cytometry, and the expression of oxidative stress, ferroptosis, and related molecules of Nrf2/ARE pathway was detected by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The mortality of primary cardiomyocytes in the H(2)O(2) group was obviously increased. Ferrostatin-1 treatment can effectively inhibit cell death, improve antioxidant enzyme activity, inhibit the expression of ferroptosis-related molecules, and activate Nrf2/ARE pathway expression. CONCLUSION: Ferroptosis-specific inhibitor ferrostatin-1 relieves H(2)O(2)-induced redox imbalance in primary cardiomyocytes through the Nrf2/ARE pathway, inhibits ferroptosis, and thereby slows cardiomyocyte death.