title: Protective Effects of D-Penicillamine on Catecholamine-Induced Myocardial Injury.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Říha
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Hašková
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Martin
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Filipský
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Kateřinská 1660/32, 121 08 Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Váňová
authors.affiliation: Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Charles University in Prague, Sokolská 581, 500 05 Hradec Králové, Czech Republic.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Vávrová
authors.affiliation: Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Charles University in Prague, Sokolská 581, 500 05 Hradec Králové, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Holečková
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Homola
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University in Prague, Kateřinská 1660/32, 121 08 Prague, Czech Republic; 4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, U Nemocnice 2, 128 02 Prague, Czech Republic.
authors.forename: Libor
authors.initials: L
authors.lastname: Vítek
authors.affiliation: Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Charles University in Prague, Sokolská 581, 500 05 Hradec Králové, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Palicka
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Šimůnek
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Přemysl
authors.initials: P
authors.lastname: Mladěnka
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D002395:Catecholamines; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007477:Ions; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010396:Penicillamine / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar; D020107:Troponin T / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D002395:Catecholamines; D007477:Ions; D007502:Iron Chelating Agents; D020107:Troponin T; D007501:Iron; D010396:Penicillamine; D003676:Deferoxamine