AJP - Heart and Circulatory Physiology, Vol 266, Issue 1 121-H127, Copyright © 1994 by American Physiological Society

ARTICLES

Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent

R. M. Byler, N. A. Sherman, J. S. Wallner and L. D. Horwitz
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.

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.

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