Fluorescence spectra of cardiac myosin and in vivo experiment: studies on daunorubicin-induced cardiotoxicity

Document Type: Original Article


Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, Engineering Technology Research Center of Biological Peptide Antidiabetics of Hubei Province, Department of Pharmaceutical Engineering, School of Life Science, Wuchang University of Technology, Wuhan, Hubei Province 430223, China


Objective(s):The objective of this study was to investigate the interaction of daunorubicin (DNR) and cardiac myosin (CM) and the changes in mice hearts to exhibit DNR-induced cardiotoxicity .
Materials and Methods:The interaction between DNR and CM was expressed using fluorescence quenching at pH 4.0-9.0 and 15-37 °C. DNR-induced cardiotoxicity was studied using in vivo experiment.  Forty groups mice were used control group in which mice were treated with DNR orally, and three DNR-treated groups in which mice were injected intraperitoneally with DNR at seven bolus doses of 2.0, 4.0, and 6.0 mg/kg body weight, respectively. Heart indices and myocardial enzyme levels were obtained by histopathological and biochemical analysis.
Results:The fluorescence quenching mechanism of DNR-CM complex was observed to be a static procedure at 20 °C (pH 7.4), and weakly acidic environment (pH 4.0-6.0) or higher temperature(30-37 °C) promoted the interaction between DNR and CM, causing variations in conformation and normal physiological functions of CM. Thermodynamic studies demonstrated that the binding of DNR to CM was a spontaneous process driven by entropy. It also indicated that hydrophobic interaction and hydrogen bonds may play essential roles in the combination of DNR with CM. In addition, 4.0-6.0 mg/kg DNR-treated mice exhibited obvious histopathological lesion, increase in myocardial enzyme level, and reductions in blood cell count.
Conclusion:Our results are valuable for better understanding the particular mode of DNR-CM interaction, and are important to have a deeper insight into the DNR-induced cardiotoxicity.


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