HYDROGEN-PEROXIDE CYTOTOXICITY IN CULTURED CARDIAC MYOCYTES IS IRON-DEPENDENT

Because of its potential importance in injury during myocardial ischem ia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was qu antitated by release of lactate dehydrogenase (LDH) or Cr-51, both of which correlated with loss of cell viability assessed by trypan blue e xclusion. The iron chelator deferoxamine (0.25-2 mM), but not equimola r iron-loaded deferoxamine, markedly reduced LDH and Cr-51 release. In jury was also prevented or attenuated by the diffusible reactive oxyge n metabolite scavengers dimethylthiourea (10-20 mM) and N-(2-mercaptop ropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl su lfoxide (200-400 mM), also reduced injury. Other scavengers that proba bly remained extracellular, superoxide dismutase and mannitol, were in effective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxici ty requires reactions catalyzed by intracellular iron.