2,3‐Butanedione monoxime does not protect cardiomyocytes under oxidative stress

Heart muscle ischemia‐reperfusion provokes a pronounced cardiomyocyte oxidative stress. In the present study, we examined a possible protective effect of the cardioprotective drug, 2,3‐butanedione monoxime (BDM), on the cultured neonatal cardiac myocytes exposed to oxidative stress induced by hypochlorous acid (HOCl), that may be formed by activated polymorphonuclear neutrophils in myocardium ischemic‐reperfusion areas, and a useful model oxidant, tert‐butyl hydroperoxide (tBHP). Using isolated rat cardiomyocytes substantial cytotoxicity of HOCl and tBHP was demonstrated: The concentrations of HOCl and tBHP causing a 50% decrease of cardiomyocyte cell viability were estimated to be 55 ± 5 µM and 36 ± 6 µM, respectively. The cell viability measured immediately after the tBHP oxidative treatment was significantly higher than that measured after 22 h of cell post‐incubation in a fresh culture medium. This showed delayed cell death after removing tBHP. Hypochlorous acid treatment of cardiomyocytes did not change cellular viability during the cellular post‐incubation in a fresh medium. Even a long‐term (22 h) incubation of oxidatively damaged cardiomyocytes with BDM (5 mM) added after the HOCl removal did not recover the viability of the HOCl‐exposed cells. In the presence of BDM, the cytotoxicity of HOCl significantly increased probably due to a direct reaction of both compounds and toxic chlorinated derivative formation. 2,3‐Butanedione monoxime (5 mM) did not reduce cytotoxicity of tBHP, either. Such well‐known antioxidative agents as melatonin or glutathione considerably prevented oxidant‐induced cell death in a concentration‐dependent manner. Copyright © 2005 John Wiley & Sons, Ltd.

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