Protein profiling in daunorubicin-induced cardiomyopathy.
The aim of this paper was to study the protein remodelling of the left ventricle following repeated administration of either daunorubicin (DNR) or DNR in combination with the cardioprotective agent dexrazoxane (DXZ). The experiment was carried out on three groups of Chinchilla male rabbits: 1. DNR (3 mg/kg i.v.), 2. DNR (3 mg/kg i.v.) + DXZ (60 mg/kg i.p.), and 3. the control group (saline 1 ml/kg i.v. in the same schedule). The drugs were given once weekly, max. 10 administrations. Protein fractions were isolated by stepwise extraction from the samples of the left ventricle. In the DNR-group, the concentrations of both, metabolic and contractile proteins were significantly reduced, while the amount of collagen was significantly higher in comparison with the control group. In the group treated with DNR and DXZ, the concentrations of individual protein fractions (except metabolic proteins) were comparable to those of the control group, which confirms a significant cardioprotective effect of DXZ. The changes of protein profiling corresponded to functional examination of both cardiac parameters (EF, dP/dt(max), PEP: LVET index) and histological examination. These data should be used in further studies dealing with evaluation of cardiotoxic and, possibly, cardioprotective effects of new drugs.
Adamcová
M
M
Institute of Physiology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic. adamcova@lfhk.cuni.cz
Pelouch
V
V
Gersl
V
V
Kaplanová
J
J
Mazurová
Y
Y
Simůnek
T
T
Klimtová
I
I
Hrdina
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D003630:Daunorubicin / Q000633:toxicity*; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D011929:Razoxane / Q000008:administration & dosage*
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D011506:Proteins; D011929:Razoxane; D003630:Daunorubicin