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 4...

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Bibliographic Details
Main Authors: Yang Liu, Chi Chen, Xiaoxiang Duan, Wenting Ma, Man Wang, Mengyi Tu, Ying Chen
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2015-12-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:http://ijbms.mums.ac.ir/pdf_6272_66fae3914304e4126c22dfc5f0b1942a.html
Description
Summary: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.
ISSN:2008-3866
2008-3874