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...
Main Authors: | , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Mashhad University of Medical Sciences
2015-12-01
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Series: | Iranian Journal of Basic Medical Sciences |
Subjects: | |
Online Access: | http://ijbms.mums.ac.ir/pdf_6272_66fae3914304e4126c22dfc5f0b1942a.html |
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. |
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ISSN: | 2008-3866 2008-3874 |