CHARACTERIZATION OF THE EFFECT OF CELL-FREE CRYOPRESERVED BIOLOGICAL AGENTS ON ANTIOXIDANT-PROOXIDANT HOMEOSTASIS IN HEART TISSUES IN A MODEL OF AUTOIMMUNE MYOCARDITIS

Abstract

Myocarditis is one of the main causes of acute and chronic heart failure, adverse ventricular remodeling and progression of dilated cardiomyopathy, life-threatening arrhythmias, and sudden cardiac death. Autoimmune myocarditis (AIM) can occur as an isolated condition in which the heart is the main (and usually the only) target organ. Immunosuppressive and antiviral therapy are currently the main therapeutic approaches to the treatment of patients with AMI. The aim of the work is to characterize the effect of cryoextract of the placenta (CEP), cryoextract of the spleen (CES), as well as the conditioned medium of mesenchymal stem cells (MSC-CM) on antioxidant-prooxidant homeostasis in heart tissues with autoimmune myocarditis in rats. Experimental studies were conducted on 42 male shuras weighing 200–220 g in accordance with the basic bioethical norms of the Helsinki Declaration of the World Medical Association. AIM was modeled according to the method of Pavlenko H.P. Cell-free biological agents were administered intramuscularly (in/m), with an interval of 2 days (a total of 5 injections), respectively, on days 14, 17, 20, 23 and 26 of the experiment. Cordarone, a myocardial repolarization inhibitor with α and β-blocking action at a dose of 10 mg/kg, was chosen as a reference drug. On the 28th day of the experiment, the animals were removed from the experiment, the heart was excised from the chest, and the content of reactants with 2-thiobarbituric acid (TBA-RP) and catalase activity in the homogenate were determined. The study showed that on the 28th day of the experiment in rats with simulated AIM, activation of lipid peroxidation (LPO) was noted, which was indicated by a statistically significant (р˂0.001) increase in the content of TBA-RP in myocardial tissues by 56.9% compared to the indicators of intact rats, which was 16.2±0.9 μmol/kg tissue, respectively. Hyperactivation of LPO in myocardial tissues and the background of AIM was accompanied by exhaustion of compensatory mechanisms, which was indicated by a decrease in catalase activity by 34.2% compared to the parameters of intact animals. The introduction of the studied cell-free biological agents led to a statistically significant decrease in the content of TBC-RP in the myocardial tissues of rats with simulated AIM, which exceeded the reference drug cordarone in terms of effectiveness, the studied indicator against the background of which application decreased by 12.4% compared to the indicators of untreated animals. According to the value of TBА-RP content relative to the parameters of untreated animals, the studied biological preparations can be placed in the following order: MSС-CM (32.7%) ˃ СES (29.2%) ˃ СEP (23.9%). The most pronounced antioxidant properties were noted against the background of the introduction of MSC-CM. Thus, the activity of catalase in rats with AIM injected with KS-MSC statistically significantly (p=0.03) increased by 40.0% compared to the indicators of animals of the control group and amounted to 2.5±0.2 μcat/kg of tissue. An integral assessment of antioxidant-prooxidant homeostasis in heart tissues on the AІM model showed that the studied cell-free cryopreserved biological agents can be arranged in the following sequence according to the expressiveness of the increase in the antioxidant-prooxidant index relative to the indicators of animals of the control group (AMI without treatment): MSC-CM (+100.0%) ˃ CEP (+65.7%) ˃ CES (+49.9%).