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

Aims 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. Results 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. Conclusion 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

The state of free-radicals procceses in cardiomyocytes in rats under the action of Doxorubicin and protection by Preductal

Aims The aim of our research work was to investigate the state of the lipid peroxidation system – the antioxidant protection system (LPO-AOS) in heart tissue in rats received either Doxorubicin alone or in combination with Preductal premedication. Materials and methods Our experimental studies were carried out in mature male albino rats from outbread stocks (the cohort covered 50 animals) with an individual body mass from 150 to 160 g. The cohort included the following groups of the rats: the reference group covered 10 intact animals; group 1 (20 rats) received dosage of Doxorubicin of 2mg/kg, five times, up to a cumulative dose of 10 mg/kg; group 2 (20 animals) medicated as follows: the 5-day introduction of Preductal with dosage of 35 mg/kg followed by Doxorubicin medication according to the same schedule used in group 1. MDA, levels of the A & E vitamins, SOD and catalase activity, Total Peroxidase Activity (TPA), the ratios E/A, SOD/TPA and SOD/catalase were assessed in heart tissue. Statistics data were processed with original software Statistica 6,0. Results The Doxorubicin medication results in a decline in antioxidant protection components: reported are a decrease in SOD by 38,7%, catalase by 23,1%, TPA by 31,3%, and the levels of vitamins of A and E by 21% and 39%, respectively. We also noted a SOD/catalase ratio decline by 21,3% and a reduction in the SOD/TPA ratio by 27% with an increase in the E/A ratio by 30.8%. The above mentioned condition of the components of the antioxidative protection of cardiomyocytes was accompanied by an accumulation of MDA therein, the level of which was reported to be 28% higher as compared with that in the intact animals. In rodents of group 2, the use of Preductal induced the normalization of activity of SOD, catalase, TPA, levels of vitamins A and E, coefficients of activity of antioxidant ferments and vitamins. The MDA level was found to be the same as it was the case with the intact rats, but at the same time it was by 31,3% lower as compared with the data recorded in the group 1 animals. Conclusion The Doxorubicin medication leads to a disorder in the performance of the physiological cascade of antioxidative ferments and vitamins in the heart tissue; it is accompanied by activation of lipid peroxidation. The target of the action of Preductal as cytoprotection is the antioxidation protection cascade as a whole that contributes to suppression of Doxorubicin-induced oxidative stress in the heart muscle