Myocardial ferroptosis promotes heart failure (HF), myocardial infarction, heart transplantation and doxorubicin-induced cardiotoxicity.22 Cardiac IRI is a critical event leading to HIF-induced transferrin receptor-1 upregulation and iron overload, reactive oxygen species generation, lipid oxidative damage and ferroptosis.36 Moreover, mitochondrial iron accumulates in rat myocardial IRI cell-permeable iron chelators decreased myocardial injury.37 Iron accumulation also induced Nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated Heme-oxygenase (Hmox) up-regulation, mitochondrial lipid peroxidation and ferroptosis in doxorubicin and IRI-induced HF.38 Myocardial Toll like receptor 4 (TLR4) and NADPH oxidase 4 (NOX4) know-down also reduced ventricular remodeling and cardiomyocyte ferroptosis in rat HF.39 Ferroptosis contribution to chronic obstructive pulmonary disease pathogenesis was demonstrated in either GPX4 deficient or overexpressing mice.40 A role of ferroptosis in hereditary hemochromatosis progressing to liver cirrhosis was hypothesized
Many disease processes, including aging, diabetes, and heart disease, are related to low glutathione levels, and because of this, glutathione supplementation is sometimes recommended to prevent or reduce the progression of these diseases
Avoiding unwanted targets: If peptide binds receptors primarily on cells not involved in disease, less likely providing benefit
PPAR, proliferator-activated receptor
