Melatonin regulates Sirt1/Nrf2/GPX4 pathway to inhibit ferroptosis and alleviate myocardial injury caused by sepsis

Figure 3 Melatonin reduces oxidative stress and ferroptosis-related proteins in mouse cardiac tissue. A: Myocardial reactive oxygen species measured by 2’,7’-dichlorodihydrofluorescein diacetate fluorescence microscopy with quantitative analysis; B-D: Cardiac malondialdehyde, glutathione, and superoxide dismutase activity; E: Representative immunoblots of glutathione peroxidase 4, NADPH oxidase 4, and acyl-CoA synthetase long-chain family member 4 in cardiac tissue (glyceraldehyde-3-phosphate dehydrogenase loading control); F: Densitometric quantification normalized to glyceraldehyde-3-phosphate dehydrogenase. Data are mean ± SD; n = 6 mice per group. One-way analysis of variance with Bonferroni post-hoc testing. ^aP < 0.01 vs control; ^bP < 0.01 vs lipopolysaccharide. ACSL4: Acyl-CoA synthetase long-chain family member 4; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GPX4: Glutathione peroxidase 4; GSH: Glutathione; LPS: Lipopolysaccharide; LPS + Mel: Lipopolysaccharide plus melatonin; LPS + Fer-1: Lipopolysaccharide plus ferrostatin-1; MDA: Malondialdehyde; Nox4: NADPH oxidase 4; ROS: Reactive oxygen species; SOD: Superoxide dismutase.