The state of free-radicals procceses in cardiomyocytes in rats under the action of Doxorubicin and protection by Preductal
* Corresponding author:
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.
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.
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.
Oleg I. Kit, Elena M. Frantsiyants, Irina V. Neskubina, Ekaterina I. Surikova, Elena V. Shalashnaya, Lyudmila A. Nemashkalova, Natalia D. Cheryarina, Olga V. Kozyuk, Yulia A. Pogorelova, Larisa S. Kozlova, Valeria A. Bandovkina, Irina V. Kaplieva, Lidia K. Trepitaki, Roman E. Myagkov, Mikhail А. Kozhushko, Sergey V. Sanamyants, Mikhail А. Averkin, Roman Е. Tolmakh. The state of free-radicals procceses in cardiomyocytes in rats under the action of Doxorubicin and protection by Preductal. Cardiometry; Issue 13; November 2018; p.48-53; DOI: 10.12710/cardiometry.2018.13.4853; Available from: http://www.cardiometry.net/issues/no13-november-2018/proccesesin-cardiomyocytes