Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper chelation are, however, sparse. The effect of the clinically used copper chelator D-penicillamine in the catecholamine model of acute myocardial injury was tested in cardiomyoblast cell line H9c2 and in Wistar Han rats. D-Penicillamine had a protective effect against catecholamine-induced injury both in vitro and in vivo. It protected H9c2 cells against the catecholamine-induced viability loss in a dose-dependent manner. In animals, both intravenous D-penicillamine doses of 11 (low) and 44 mg/kg (high) decreased the mortality caused by s.c. isoprenaline (100 mg/kg) from 36% to 14% and 22%, respectively. However, whereas the low D-penicillamine dose decreased the release of cardiac troponin T (specific marker of myocardial injury), the high dose resulted in an increase. Interestingly, the high dose led to a marked elevation in plasma vitamin C. This might be related to potentiation of oxidative stress, as suggested by additional in vitro experiments with D-penicillamine (iron reduction and the Fenton reaction). In conclusion, D-penicillamine has protective potential against catecholamine-induced cardiotoxicity; however the optimal dose selection seems to be crucial for further application.

Department of Biochemical Sciences Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Pharmacognosy Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Charles University Prague Sokolská 581 500 05 Hradec Králové Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University Prague Kateřinská 1660 32 121 08 Prague Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University Prague Kateřinská 1660 32 121 08 Prague Czech Republic; 4th Department of Internal Medicine 1st Faculty of Medicine Charles University Prague U Nemocnice 2 128 02 Prague Czech Republic

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