Investigation of cardiotoxic effect of A-1 apo + D actinomycin complex on isolated rat heart
Автор: Knyazev Roman A., Trifonova N.V., Kolpakov A.R., Polyakov L.M.
Журнал: Патология кровообращения и кардиохирургия @journal-meshalkin
Рубрика: Экспериментальные статьи
Статья в выпуске: 4 т.20, 2016 года.
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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.
Аполипопротеин а-i, isolated rat heart, apolipoprotein a-i, actinomycin d, cardiotoxicity
Короткий адрес: https://sciup.org/142140773
IDR: 142140773 | DOI: 10.21688-1681