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

Document Type: Original Article

Authors

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

Abstract

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.

Keywords


1. Lowey S, Risby D. Light chains from fast and slow muscle myosins. Nature 1971; 234: 81-85.

2. Teerlink JR.  A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail Rev 2009; 14:289-298.

3. Jacques AM, Briceno N, Messer AE, Gallon CE, Jalilzadeh S, Garcia E, et al. The molecular phenotype of human cardiac myosin associated with hypertrophic obstructive cardiomyopathy. Cardiovasc Res 2008; 79:481-491.

4. Van Driest SL, Jaeger MA, Ommen SR, Will ML, Gersh BJ, Tajik AJ, et al. Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2004; 44:602-610.

5. Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, et al. Cardiac myosin missense mutations cause dilated cardiomyopathy in mouse models and depress molecular motor function. Proc Natl Acad Sci USA 2006; 103:14525-14530.

6. Gupta MP. Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure. J Mol Cell Cardiol 2007; 43:388-403.

7. Kessler–lecklon G. Effect of triiodothyronine on cultured neonatal rat heart cells: beating rate, myosin subunits and CK-isozymes. J Mol Cell Cardiol 1988; 20:649-655.

8. Shalitin N, Friedman M, Schlesinger H, Barhum Y, Levy MJ, Schaper W, et al. The effect of angiotensin Ⅱ on myosin heavy chain expression in cultured  myocardial cells. In Vitro Cell Dev Biol Anim 1996; 32:573-578.

9. Petre CE, Dittmer DP. Liposomal daunorubicin as treatment for Kaposi’s sarcoma. Int J Nanomed 2007; 2:277-288.

10. Behal V. Bioactive products from Streptomyces. Adv Appl Microbiol 2000;47:113-156.

11. Todeschini G, Tecchio C, Meneghini V, Pizzolo G, Veneri D, Zanotti R, et al. Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin. Leukemia 1998; 12:144-149.

12. Cusack BJ, Young SP, Gambliel H, Olson RD. Effect of aging on cardiac contractility in a rat model of chronic daunorubicin cardiotoxicity. Cardiovasc Toxicol 2002; 2:99-109.

13. Clavio M, Venturino C, Pierri I, Garrone A, Miglino M, Canepa L, et al. Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia. Ann Hematol 2004; 83:696-703.

14. Saad SY, Najjar TA, Arafah MM. Cardioprotective effects of subcutaneous ebselen against daunorubicin-induced cardiomyopathy in rats. Basic ClinPharmacol 2006; 99: 412-417.

15. Simunek T, Sterba M, Popelova O. Anthracycline induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 2009; 61: 154-171.

16. Simunek T, Klimtova I, Kaplanova J, Sterba M, Mazurova Y, Adamcova M, et al. Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits. Pharmacol Res 2005; 51:223-231.

17. Santos DL, Moreno AJ, Leino RL, Froberg MK, Wallace KB. Carvedilol protects against doxorubic induced mitochondrial cardiomyopathy. Toxicol Appl Pharmacol 2002; 185: 218-227.

18. Eidenschink AB, Schroter G, Muller-Weihrich S, Stern H. Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in childhood. Cardiol Young 2000; 10:610-617.

19. Lemmens K, Segers VF, Demolder M, De Keulenaer GW. Role of neuregulin-1/ErbB2 signaling in endothelium-cardiomyocyte cross-talk. J Biol Chem 2006; 281:19469-19477.

20. Kim E, Tam M, Siems WF, Kang C. Effects of drugs with muscle-related side effects and affinity for calsequestrin on the calcium regulatory function of sarcoplasmic reticulum microsomes. Mol Pharmacol 2005; 68:1708-1715.

21. Charlier HA Jr, Olson RD, Thornock CM, Mercer WK, Olson DR, Broyles TS, et al. Investigations of calsequestrin as a target for anthracyclines: comparison of functional effects of daunorubicin, daunorubicinol and trifiuoperazine. Mol Pharmacol 2005; 67:1505-1512.

22. Menna P, Minotti G, Salvatorelli E. In vitro modeling of the structure activity determinants of anthracycline cardiotoxicity. Cell Biol Toxicol 2007; 23:49-62.

23. Albani JR. Correlation between dynamics, structure and spectral properties of human α1-acid glycoprotein (orosomucoid): a fluorescence approach. Spectrochim ActaA Mol Biomol Spectrosc 1998; 54:175-183.

24. Liu Y, Lin A, Sun X, Li B. Effect of zinc and copper on the interaction of daunorubicin with cardiac myosin. Biol Trace Elem Res 2008; 126:106-114.

25. Liu Y, Li B, Sun X, Lin A, Wang D. Effect of selenium on the interaction between daunorubicin and cardiac myosin. Biol Trace Elem Res 2012; 147:240-245.

26. Liu Y, Wang D. Administration of chromium (III) and manganese (II) as a potential protective approach against daunorubicin-induced cardiotoxicity: in vitro and in vivo experimental evidence. Biol Trace Elem Res 2013; 156:253-261.

27. Liu Y, Li B, Sun X, Lin A. Isolation and fluorescence spectrum of cardiac myosin from pig heart. Protein J 2009; 28:167-174.

28. Zhao N, Wang XM, Pan HZ, Hu YM, Ding LS. Spectroscopic studies on the interaction between tryptophan–erbium (III) complex and herring sperm DNA. Spectrochim Acta A  2010; 75:1435-1442.

29. Yoshioka K, Enaga S, Taniguchi K, Fukushima U, Uechi M, Mutoh K. Morphological characterization of ductular reactions in canine liver disease. J Comp Pathol 2004; 130:92-98.

30. Liu Y, Xie MX, Jiang M, Wang YD. Spectroscopic investigation of the interaction between human serum albumin and three organic acids. Spectrochim Acta A 2005; 61:2245-2251.

31. Suzukida M, Le HP, Shahid F, Mcpheraon RA, Birnbaum ER. Resonance energy transfer between cysteine-34 and tryptophan-214 in human serum albumin distance measurements as function of pH. Biochemistry 1983; 22:2415-2420.

32. Zhang SF, Sun XJ, Qu FL, Kong RM. Molecular spectroscopic studies on the interaction of ferulic acid with calf thymus DNA. Spectrochim Acta A 2013; 112:78-83.

33. Hemmateenejad B, Yousefinejad S. Interaction study of human serum albumin and ZnS nanoparticles using fluorescence spectrometry. J Mol Struct 2013; 1037:317-322.

34. Monti S, Ottani S, Manoli F, Manet I, Scagnolari F, Zambell B, et al. Chiral recognition of 2-(3-benzoylphenyl) propionic acid (ketoprofen) by serum albumin: an investigation with microcalorimetry, circular dichroism and molecular modeling. Phys Chem Chem Phys 2009; 11:9104-9113.

35. Lakowicz JR. Principles of fluorescence spectro-scopy. New York: Berlin Heidelberg; 2006.

36. Zhang GW, Fu P, Wang L, Hu MM. Molecular spectroscopic studies of farrerol interaction with calf thymus DNA. J Agric Food Chem 2011; 59:8944-8952.

37. Bi SY, Zhang HQ, Qiao CY, Sun Y, Liu CM. Studies of interaction of emodin and DNA in the presence of ethidium bromide by spectroscopic method. Spectrochim Acta A 2008; 69: 123-129.

38. Yuan JL, Liu H, Kang X, Lv Z, Zou GL. Characteristics of the isomeric flavonoids apigenin and genistein binding to hemoglobin by spectroscopic methods. J Mol Struct 2008; 891:333-339.

39. Lu Y, Lv J, Zhang GS, Wang GK, Liu QF. Interaction of an anthracycline disaccharide with ctDNA: Investigation by spectroscopic technique and modeling studies.
Spectrochim Acta A 2010; 75:1511-1515.

40. Cui FL, Qin LX, Zhang GS, Yao XJ, Du J. Binding of daunorubicin to human serum albumin using molecular modeling and its analytical application. Int J Biol Macromol 2008; 42:221-228.

41. Souid AK, Tacka KA, Galvan KA, Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem Pharm 2003; 66:977-987.

42. Messori L, Piccioli F, Gabrielli S, Orioli P, Angeloni L, Bugno CD. The disaccharide anthracyclineMEN 10755 binds human serum albumin to a non-classical drug binding site. Bioorg Med Chem 2002; 10:3425-3430.

43. Bristow MR, Billingham ME, Mason JW, Daniels JR. Clinical spectrum of anthracycline antibiotic cardiotoxicity. Cancer Treat Rep 1978; 62:873-879.

44. Hale JP, Lewis IJ. Anthracyclines: cardiotoxicity and its prevention. Arch Dis Child 1994; 71:457-462.

45. Franken NA, Strootman E, Hollaar L, van der Laarse A, Wondergem J. Myocardial enzyme activities in plasma after whole-heart irradiation in rats. J Cancer Res Clin Oncol 2000; 126:27-32.

46. Cao Y, Kennedy R, Klimberg VS. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res 1999; 85:178-182.

47. Saad SY, Najjar TA, Al-Rikabi AC. The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats. Pharmacol Res 2001; 43: 211-218.

48. Saad SY, Najjar TA, Alashari M. Cardiotoxicity of doxorubicin/paclitaxel combination in rats: Effect of sequence and timing of administration. J Biochem Mol Toxicol 2004; 18: 78-86.

49. Fichtner I, Arndt D, Elbe B, Reszka R. Cardiotoxi-city of free and liposomally encapsulated rubomycin (daunorubicin) in mice. Oncology 1984; 41:363-369.