title: Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent.
abstract: Because of its potential importance in injury during myocardial ischemia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was quantitated by release of lactate dehydrogenase (LDH) or 51Cr, both of which correlated with loss of cell viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25-2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and 51Cr release. Injury was also prevented or attenuated by the diffusible reactive oxygen metabolite scavengers dimethylthiourea (10-20 mM) and N-(2-mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl sulfoxide (200-400 mM), also reduced injury. Other scavengers that probably remained extracellular, superoxide dismutase and mannitol, were ineffective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions catalyzed by intracellular iron.
authors.affiliation: Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: R M
authors.initials: RM
authors.lastname: Byler
authors.forename: N A
authors.initials: NA
authors.lastname: Sherman
authors.forename: J S
authors.initials: JS
authors.lastname: Wallner
authors.forename: L D
authors.initials: LD
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D002470:Cell Survival; D002474:Cell-Free System; D002478:Cells, Cultured; D002642:Chick Embryo; D004058:Diffusion; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007501:Iron / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D008625:Tiopronin / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D008625:Tiopronin; D007501:Iron; D013890:Thiourea; D004121:Dimethyl Sulfoxide