title: 2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress.
abstract: 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 microM and 36 +/- 6 microM, 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.
authors.affiliation: Department of General Biophysics, University of Lodz, Lodz, Poland. tomaszp@biol.uni.lodz.pl
authors.forename: T
authors.initials: T
authors.lastname: Przygodzki
authors.forename: E
authors.initials: E
authors.lastname: Lapshina
authors.forename: I
authors.initials: I
authors.lastname: Zavodnik
authors.forename: A
authors.initials: A
authors.lastname: Sokal
authors.forename: M
authors.initials: M
authors.lastname: Bryszewska
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000633:toxicity; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D004791:Enzyme Inhibitors; D019188:Organ Preservation Solutions; D016877:Oxidants; C004717:diacetylmonoxime; D006997:Hypochlorous Acid; D020122:tert-Butylhydroperoxide; D003931:Diacetyl