Антрациклінові ушкодження серця та вплив кріоекстракту плаценти на стан міокарда при доксорубіциновій кардіоміопатії

Abstract

Doxorubicin is the most widely used drug among anthracyclines. However, despite its clinical effectiveness, the cardiotoxic effect is observed in approximately 25,0% of patients, thus limiting its use. Although significant success in understanding individual pathogenetic elements of the cardiotoxic effect of this drug has been achieved, cancer patients who have doxorubicin-induced cardiac complications are currently treated mostly with drugs for cardiac insufficiency because there is no specific treatment for anthracycline cardiomyopathy.

Purpose – to characterize the effect of placenta cryoextract on the course of doxorubicin myocardial injury on the model of chronic doxorubicin cardiomyopathy compared to reference drug vinboron according to the data of biochemical analyses of the heart tissues.

Materials and methods. Chronic doxorubicin cardiomyopathy was modeled by the means of injection of doxorubicin hydrochloride at the rate of 5 mg/kg of body weight once a week for 4 weeks (on days 7, 14, 21, 28). The placenta cryoextract was injected on days 1, 7, 14, 21, 28. The animals were withdrawn from the experiment on day 35. The content of adenylic nucleotides, glycogen, pyruvate, lactate, and reactants with thiobarbituric acid was studied in the homogenates of the heart tissues.

Results and discussion. The development of doxorubicin cardiomyopathy is accompanied with impaired energy metabolism in the myocardium of animals, as indicated by a statistically significant decrease in the content of adenosine triphosphoric acid (ATP) (p < 0,01) in myocardium tissues by 42,4% and an increase in the content of adenosine diphosphoric acid (ADP) (р < 0,05) and adenosine monosphoric acid (AMP) (p < 0,001) by 45,4% and by 2,2 times respectively relative to the parameters of intact rats. The development of energy disbalance is accompanied with a statistically significant (p< 0,001) increase in the content of reactants with thiobarbituric acid. The use of placenta cryoextract leads to nullifying the energy deficit in myocardium of animals with doxorubicin cardiomyopathy – the level of ATP in the setting of injection of the studied cryoextract increased statistically significantly (p < 0,001) by 72,7%. In addition, in the setting of injection of the studied cryoextract, the «lactate/pyruvate» ratio decreased statistically significantly by 51,9% relative to the parameters of the animals with doxorubicin cardiomyopathy which did not receive treatment and the level of glycogen increased statistically significantly (р < 0,01) by 2 times relative to the parameters of the rats with doxorubicin cardiomyopathy which did not receive treatment, but the content of reactants with thiobarbituric acid decreased (p < 0,05) by 38,9%.

Conclusions. Placenta cryoextract shows cardioprotective activity, which is compared to is meant to be used when you’re highlighting similarities, while compared with is supposed to be used when you’re focusing on the differences vinboron, on the model of doxorubicin cardiomyopathy. One of the mechanisms of the mentioned activity is the ability of the studied cryoextract to produce an energystabilizing effect on cardiomyocytes, and also its antioxidative activity.