Vol. 20 No. 4 (2016)
EXPERIMENTAL STUDIES

Investigation of cardiotoxic effect of A-1 apo + D actinomycin complex on isolated rat heart

PDF (Русский)
  • R. Knyazev,
  • N. Trifonova,
  • A. Kolpakov,
  • L. Polyakov
R. Knyazev
Research Institute of Biochemistry, 630117, Novosibirsk, Russian Federation
Bio
N. Trifonova
Research Institute of Biochemistry, 630117, Novosibirsk, Russian Federation
A. Kolpakov
Research Institute of Biochemistry, 630117, Novosibirsk, Russian Federation; Novosibirsk State Medical University, Ministry of Health Care of Russian Federation, 630091, Novosibirsk, Russian Federation
L. Polyakov
Research Institute of Biochemistry, 630117, Novosibirsk, Russian Federation
DOI: https://doi.org/10.21688/1681-3472-2016-4-88-95

Published 2016-12-30

Keywords

  • isolated rat heart,
  • apolipoprotein A-I,
  • actinomycin D,
  • cardio toxicity

How to Cite

Knyazev, R., Trifonova, N., Kolpakov, A., & Polyakov, L. (2016). Investigation of cardiotoxic effect of A-1 apo + D actinomycin complex on isolated rat heart. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 20(4), 88–95. https://doi.org/10.21688/1681-3472-2016-4-88-95

Copyright (c) 2016 Knyazev R.A., Trifonova N.V., Kolpakov A.R., Polyakov L.M.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Aim. Chemotherapy is one of the main methods of treating malformations. However, this technique causes a great deal of side effects, among which are complications related to cardiac toxicity. Development of new anticancer drugs is directly related to a decrease in the general toxic effect on the organism and the cardiovascular system in particular. The aim of the study was to investigate the capability of apolipoprotein A-1 together with an anticancer drug, actinomycin D, to induce functional disturbances in the performance of an isolated rat heart and to compare the effect with that of pure actinomycin D.
Methods. For experiments use was made of Wistar male rats weighing 220-250 g. A modified Krebbs-Henseleit buffer saturated with carbogene (95 % O2 and 5 % CO2, solution temperature 37.5 °C) was used as perfusate. Experiments were conducted on isolated rat hearts. The isolated rat hearts were perfused retrogradely by a standard procedure, with isovolumic pressure registered in the left ventricle. Apolipoprotein A-I was isolated of human high-density lipoprotein by delipidating followed by separation of the proteins mix by means of column chromatography. In the experiment, apolipoprotein A-I- was mixed with actinomycin D, with concentration of the anticancer drug in the complex being 0.1 µg/ml.
Results. Actinomycin D with concentration 1 µg/ml aggravates the functional indicators of the heart and enhances energy load on the myocardium. Decreasing the concentration of cytostatic down to 0.1 µg/ml of perfusate brings the indicators to the baseline values. Apolipoprotein A-I combined with actinomycin D offsets the changes introduced by the cytostatic without a carrier. The complex improves hemodynamics, which can be interpreted by the presence of a protein component.
Conclusion. An isolated rat heart model shows that apolipoprotein A-I in combination with 0.1 µg/ml actinomycin D does not cause cardio toxicity. The complex improves myocardial efficiency through the use of the protein component as a carrier of the anticancer drug.

Received 15 November 2016. Accepted 30 November 2016.

Funding: The research was supported by the federal budget project implemented by Research Institute of Biochemistry, Reg. R-085.
Conflict of interest: The authors declare no conflict of interest.
Author contributions
Conceptualization and study design: Kolpakov AR.
Сбор и обработка материала: Knyazev R.A., Trifonova N.V.
Statistical data processing: Knyazev R.A.
Article writing: Knyazev R.A.
Review & editing: Polyakov L.M.

PDF (Русский)

References

  1. Geoffrey S, Symmans F, Pusztai L, Gabriel N. Targeted therapies for cancer 2004. American journal of clinical pathology. 2004;122(4):598-609. http://dx.doi.org/10.1309/5CWP-U41A-FR1V-YM3F
  2. Glickson JD, Lund-Katz S, Zhou R, Choi H, Chen IW, Li H, Corbin I, Popov AV, Cao W, Song L, Qi C, Marotta D, Nelson DS, Chen J, Chance B, Zheng G. Lipoprotein nanoplatform for targeted delivery of diagnostic and therapeutic agents. Molecular imaging. 2008;7(2):101-10.
  3. Knyazev RA, Trifonova NV, Polyakov LM. Study the ability of high-density lipoprotein and Apolipoprotein A-I bind and transport of anticancer drugs in Ehrlich ascites carcinoma cell. Mezhdunarodnyy zhurnal prikladnykh i fundamental'nykh issledovaniy. 2015;(11-4):538-42. (In Russ.)
  4. Tverdokhleb NV, Knyazev RA, Polyakov LM. Influence Apolipoprotein A-I in complex with Actinomycin D on biosynthesis DNA in Ehrlich ascites carcinoma cells. Sovremennaya biologiya: aktualnye voprosy. 2014:52-5. (In Russ.)
  5. Fandeev OA, Vasechkin SS, Alekhin MN, Odintsov SV, Kallistov VE, Sidorenko BA. Clinical Value of Antracycline Toxicity: Modern Approaches to Diagnosis, Prevention, and Treatment. Kardiologiya. 2011;(7):40-6. (In Russ.)
  6. Kolpakov AR, Knyazev RA, Trifonova NV, Polyakov LM. The cardiotonic properties of human Apolipoprotein A-I. Ateroskleroz. 2015;11(4):20-4. (In Russ.)
  7. Polyakov LM, Sumenkova DV, Knyazev RA, Panin LE. The analysis of interaction lipoproteins and steroid hormones. Biochemistry (Moscow). Supplement Series B: Biomedical Chemistry. 2010;4(4):362-5. http://dx.doi.org/10.1134/S1990750810040062
  8. Siboni RB, Nakamori M, Wagner SD, Struck AJ, Coonrod LA, Harriott SA, Cass DM, Tanner MK, Berglund JA. Actinomycin D Specifically Reduces Expanded CUG Repeat RNA in Myotonic Dystrophy Models. Cell reports. 2015;13(11):2386-94. http://dx.doi.org/10.1016/j.celrep.2015.11.028
  9. Cortes CL, Veiga SR, Almacellas E, Hernández-Losa J, Ferreres JC, Kozma SC, Ambrosio S, Thomas G, Taule A. Effect of low doses of actinomycin D on neuroblastoma cell lines. Molecular cancer. 2016;15:1. http://dx.doi.org/10.1186/s12943-015-0489-8
  10. Berezovskaya IV, Gorbunova TV, Postnikova TV. Comparative Сharacteristics of Toxicity Kosmegena and Aknomida-D in the Treatment of Solid Tumors in Children. Onkopediatriya = Oncopediatrics. 2014;(1):20-4. (In Russ.)
  11. DiSalvo TG, Narula J, Cosimi AB, Keck S, Dec GW, Semigran MJ. Actinomycin D is an effective adjunctive immunosuppressive agent in recurrent cardiac allograft rejection. J Heart Lung Transplant. 1995;14(5):955-62.
  12. Varga E, Nagy N, Lazar J, Czifra G, Bak I, Biro T, Tosaki A. Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release. Life Sci. 2004;75(20):2411-23. http://dx.doi.org/10.1016/j.lfs.2004.04.031
  13. Lu D, Wang Y, Li Ch, Wei G, Chen R, Dong D, Yao M. Actinomycin D inhibits cell proliferations and promotes apoptosis in osteosarcoma cells. Int J Clin Exp Med. 2015;8(2):1904-11.