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The state of hydrolytic processes in the myocardium and its draining lymphocytes in rats under the effect of Doxorubicin under protective Trimetazidine premedication

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The aim hereof is to study the activity of cathepsin D (CatD), alkaline phosphatase (ALP) and acid phosphatase (AP), the antitryptic activity (ATA) of acid-stable inhibitors (ASI) in rats in heart tissue and its draining lymphocytes under introduction of Doxorubicin and protection with Trimetazidine.

Materials and methods

The study has been carried out in outbred male rats (50 animals) weighing 150-160 g: the reference group consists of 10 animals; group 1 (20 animals) has experienced injections of Doxorubicin in physiological saline at a dose of 2 mg/kg, 5 times; group 2 (20 animals) has undergone the above mentioned Doxorubicin medication after preliminary protection with Trimetazidine for 5 days at a dose of 35 mg/kg. In the myocardium and its draining lymphocytes determined has been the following: CatD, ATA, ASI, ALP, AP, ratios CatD/ATA, CatD/ASI and AP/ALP. The statistical significance has been evaluated using the Mann-Whitney criterion.


In the group 1 animals in their myocardia and lymphocytes observed has been a statistically significant increase in the activity of CatD by 42.4 and 64.6%, respectively, AP and ALP by 2.22.3 times on the average, ASI and ATA by 1.8-1,9 times if to compare with the level in the reference animals. Ratios CatD/ ATA, CatD/ASI in the myocardium have been considerably decreased by 25.4% and 24.2%, and in the lymphocytes all the ratios remained at the level of values in the reference animals. In group 2 in the myocardia and lymphocytes a significant decrease in enzyme activity by 23-31%, on the average, as compared with reference animals, has been observed, and, at the same time, all the ratios have been at the level of the reference animals.


The dynamics of the studied indicators recorded for the hearts in the group 1 rats reflect an intensification of catabolic processes and the activation of inflammation in myocardial tissue as a manifestation of the toxic effect of Doxorubicin. The dynamics of indicators in the group 2 rats demonstrates the lack of activation in the processes of autophagy/apoptosis and the absence of a pronounced local inflammation that is caused by the cardioprotective action of Trimetazidine.


Elena М. Frantsiyants, Ekaterina I. Surikova, Irina V. Kaplieva, Lidia K. Trepitaki, Irina V. Neskubina, Elena V. Shalashnaya, Valeria A. Bandovkina, Larisa S. Kozlova, Yulia A. Pogorelova, Lyudmila A. Nemashkalova, Natalia D. Cheryarina, Irina S. Tavaryan, Olga V. Kozyuk, Lyudmila Y. Rozenko, Pavel G. Sakun, Vladimir S. Trifanov. The state of hydrolytic processes in the myocardium and its draining lymphocytes in rats under the effect of Doxorubicin under protective Trimetazidine premedication. Cardiometry; Issue 13; November 2018; p.66-74; DOI: 10.12710/cardiometry.2018.13.6674; Available from:


Cardiotoxicity,  Doxorubicin,  Trimetazidine,  Cathepsin D,  Acid phosphatase,  Alkaline phosphatase
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