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A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin
Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic
Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, Brno CZ-616 00, Czech Republic
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Komenskeho namesti 2, Brno CZ-662 43, Czech Republic
Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, V Uvalu 84, Prague 5 CZ-15006, Czech Republic
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, Prague 2 CZ-12840, Czech Republic
* Author to whom correspondence should be addressed.
Received: 29 August 2013; in revised form: 26 September 2013 / Accepted: 9 October 2013 / Published: 31 October 2013
Abstract: Doxorubicin is a commonly used antineoplastic agent in the treatment of many types of cancer. Little is known about the interactions of doxorubicin with cardiac biomolecules. Serious cardiotoxicity including dilated cardiomyopathy often resulting in a fatal congestive heart failure may occur as a consequence of chemotherapy with doxorubicin. The purpose of this study was to determine the effect of exposure to doxorubicin on the changes in major amino acids in tissue of cardiac muscle (proline, taurine, glutamic acid, arginine, aspartic acid, leucine, glycine, valine, alanine, isoleucine, threonine, lysine and serine). An in vitro interaction study was performed as a comparison of amino acid profiles in heart tissue before and after application of doxorubicin. We found that doxorubicin directly influences myocardial amino acid representation even at low concentrations. In addition, we performed an interaction study that resulted in the determination of breaking points for each of analyzed amino acids. Lysine, arginine, β-alanine, valine and serine were determined as the most sensitive amino acids. Additionally we compared amino acid profiles of myocardium before and after exposure to doxorubicin. The amount of amino acids after interaction with doxorubicin was significantly reduced (p = 0.05). This fact points at an ability of doxorubicin to induce changes in quantitative composition of amino acids in myocardium. Moreover, this confirms that the interactions between doxorubicin and amino acids may act as another factor most likely responsible for adverse effects of doxorubicin on myocardium.
Keywords: myocardium; cardiomyopathy; interaction; amide bond; spectrophotometry; ion-exchange liquid chromatography
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Heger, Z.; Cernei, N.; Kudr, J.; Gumulec, J.; Blazkova, I.; Zitka, O.; Eckschlager, T.; Stiborova, M.; Adam, V.; Kizek, R. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin. Int. J. Mol. Sci. 2013, 14, 21629-21646.
Heger Z, Cernei N, Kudr J, Gumulec J, Blazkova I, Zitka O, Eckschlager T, Stiborova M, Adam V, Kizek R. A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin. International Journal of Molecular Sciences. 2013; 14(11):21629-21646.
Heger, Zbynek; Cernei, Natalia; Kudr, Jiri; Gumulec, Jaromir; Blazkova, Iva; Zitka, Ondrej; Eckschlager, Tomas; Stiborova, Marie; Adam, Vojtech; Kizek, Rene. 2013. "A Novel Insight into the Cardiotoxicity of Antineoplastic Drug Doxorubicin." Int. J. Mol. Sci. 14, no. 11: 21629-21646.