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Updated: Aug 26, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Protein profiling in daunorubicin-induced cardiomyopathy
M Adamcová1, V Pelouch, V Gersl
1Institute of Physiology, Faculty of Medicine in Hradec Králové, Charles University in Prague, Hradec Králové, Czech Republic. adamcova@lfhk.cuni.cz
Abstract:
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.
Insights
Daunorubicin (DNR) damages heart muscle by altering protein levels. Dexrazoxane (DXZ) protects the heart from DNR-induced protein remodelling, preserving cardiac function.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Daunorubicin (DNR) is a chemotherapy agent with known cardiotoxicity.
- Protein remodelling in the left ventricle is a key indicator of cardiac damage.
- Dexrazoxane (DXZ) is an established cardioprotective agent used to mitigate chemotherapy-induced cardiotoxicity.
Purpose of the Study:
- To investigate the effects of repeated daunorubicin (DNR) administration on left ventricular protein remodelling.
- To evaluate the cardioprotective efficacy of dexrazoxane (DXZ) against DNR-induced protein alterations in the heart.
- To correlate protein profiling changes with cardiac function and histology.
Main Methods:
- Three groups of Chinchilla male rabbits were used: DNR alone, DNR + DXZ, and control (saline).
- Drugs were administered weekly for a maximum of 10 doses.
- Left ventricular protein fractions were isolated via stepwise extraction.
- Cardiac function was assessed using ejection fraction (EF), dP/dt(max), and PEP:LVET index.
- Histological examination was performed.
Main Results:
- DNR administration significantly reduced metabolic and contractile proteins and increased collagen in the left ventricle.
- Co-administration of DXZ with DNR resulted in protein fraction concentrations comparable to the control group.
- Dexrazoxane (DXZ) demonstrated a significant cardioprotective effect by preventing DNR-induced protein remodelling.
- Protein changes correlated with functional and histological findings.
Conclusions:
- Repeated daunorubicin (DNR) exposure causes significant detrimental protein remodelling in the heart.
- Dexrazoxane (DXZ) effectively mitigates DNR-induced cardiotoxicity by preserving normal protein profiles.
- These findings support the role of DXZ in protecting cardiac function during chemotherapy and provide a basis for evaluating new cardioprotective agents.
