Fig. 6

MMA-induced myocardial injury could be alleviated by ferroptosis inhibitor. In vitro, AC16 cells were treated with MMA (17.5 mM) alone for 3 h or with NAC (5 mM) for 2 h followed by MMA (17.5 mM) for 3 h. Otherwise, cells were treated by MMA (17.5 mM) with Ferrostatin-1 (Fer-1) (2 μM) or (1S,3R)-RSL3 (RSL3) (3 μM) for 3 h. In vivo, mice were assigned to the sham operation or myocardial I/R injury group. MMA (400 mg/kg/d) was administered seven days before the I/R injury. Meanwhile, NAC (300 mg/kg), Fer-1 (10 mg/kg​), and RSL3 (10 mg/kg​) were administered once in two days for three times before the I/R model (on day 2, 4, and 6 of the administration process). a Cell viability was detected by MTT assay after beinig administered with dimethyl sulfoxide (DMSO) as a control, MMA (15 mM), NAC (5 mM), Fer-1 (2 μM) or RSL3 (3 μM) (n = 3/group). b-d Western blot analysed of GPX4 and SLC7A11 in mice heart tissue (n = 3/group). e–g Representative images of heart sections with TTC/Evans staining and the ratios of the AAR to LV area and infarct area to AAR (n = 3/group). The area of AAR was marked with yellow dotted line. h TEM analysis of mitochondria in mice heart tissue. Yellow arrows indicate mitochondria (Scale bar: 1/2 μm). i-k Representative images of M-mode echocardiograms and quantitative analysis of EF and FS by echocardiography (n = 6/group). Data are expressed as the mean ± standard deviation. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and n.s, not significant