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

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 ۴.۰-۹.۰ and ۱۵-۳۷ °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 ۲.۰, ۴.۰, and ۶.۰ 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 ۲۰ °C (pH ۷.۴), and weakly acidic environment (pH ۴.۰-۶.۰) or higher temperature(۳۰-۳۷ °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, ۴.۰-۶.۰ 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.

Keywords:

Cardiac myosin , Cardiotoxicity , Daunorubicin , Fluorescence quenching , Myocardial enzyme