Iron-catalyzed reactions cause lipid peroxidation in the intact heart

The chemical targets and mechanisms of iron-catalyzed oxidative injury in myocardium are poorly understood. Oxygen metabolites, in the presence of iron, can initiate free-radical chain reactions in unsaturated membrane lipids, generating lipid peroxides and causing membrane injury. We examined whether exposure to iron-catalyzed oxidative injury would increase myocardial lipid peroxide levels as injury evolved in the intact heart. Isolated, buffer perfused rabbit hearts were exposed for 30 min to 100 uM Fe2+/500 uM ADP and 10 uM H2O2 (IRON group, n = 5), saline vehicle (CON group, n = 6) or 500 uM ADP and 10 uM H2O2 without iron (ADP, n = 5). Lipid peroxides were measured in cytosol and membrane fractions by a new method, using the lipid peroxide-induced oxidation of exogenous GSH to GSSG, catalyzed by the enzyme glutathione peroxidase. The results indicated that iron-catalyzed lipid peroxidation occurs in the intact heart during chemically-mediated oxidative injury.