Effect of a New Class of Compounds of the Group of Substituted 5R1, 6H2-1,3,4-thiadiazine-2-amines on the Inflammatory and Cytokine Response in Experimental Myocardial Infarction

Abstract

This study investigated the effects of the L-17 compound of the group of substituted 5R1, 6H2- 1,3,4-thiadiazine-2-amines on the immune response and the plasma level of circulating cytokines in acute myocardial infarction (MI) in rats. The study was based upon experimental work which demonstrated the role of local and systemic inflammatory reactions in MI. Acute MI in rats was induced by left coronary artery coagulation. Histological study of the myocardium sections has been carried out at the 1(th) and 7(th) days of the experimental myocardial infarction. Serum activity of creatine phosphokinase (CPK), aspartate aminotransferase (AST), isoenzymes 1 and 2 and lactate dehydroge nase (LDH1-2) were investigated at days 1(st)and 7(th). ELISA analysis for plasma cytokine levels was performed using commercially available test kits following the manufacturer's instructions. Biochemical analysis in animals with the administration of the L-17 compound after MI showed that the AST and CPK levels at days 5 and 7 of experiments did not differ significantly from the values of intact animals. In animals of the group with MI without the administration of the L-17 compound, the IL-1 level 8 times and the TNF level 7.8 times exceeded the normal indicators, while the use of L-17 compound in the therapy resulted in only 1.8 times increase of IL-1 level and 4.7 times increase of TNF level in comparison with the norm. Thus, the introduction of L-17 compound in case of experimental MI delays exudative/alternative phase of inflammation, accelerates granulocytic and decreased the inflammation and anti-inflammation interleukins level.

Immunomodulatory Action of Substituted 1,3,4-Thiadiazines on the Course of Myocardial Infarction

“…While the stress response and the immune systems are different parts of the larger defensive system [ 10 ], some might discover some immunomodulatory effects, and vice versa. This concept was confirmed by the series of studies [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ] and found confirmation in the current studies [ 96 , 97 , 112 ]. Thus, it was found that several chemical compounds of the group of substituted thiadiazines possessed the attributes of atypical antipsychotics, having a significant effect on the behavior of animals and the course of the stress reaction [ 54 , 88 ].…”

“…Modelling of MI in rats was performed in accordance with the authors’ modification of standard ligation model. Histological, biochemical and immunobiochemical studies were performed at days 1, 5, 7 and 14 of the experiment [ 96 , 97 ].…”

“…Administration of L-17 compound also led to the earlier and more active reparative process in the affected area. Thus, in control animals, the signs of formation of granulation tissue were revealed only on the seventh day and only in the structures adjacent to the necrotic zone, while on the background of L-17 compound administration, the granulation tissue had appeared in the zone of subacute inflammation by the fifth day of the experiment and had replaced the infarction zone almost completely by the seventh day, with endothelial capillary cells involved in the formation of sinusoidal capillaries, appearing on the fifth day [ 96 , 97 ]. The observed histological picture indicated that the administration of L-17 compound in MI, decreasing the entry of neutrophils into the inflammation zone and increasing the supply of macrophages, revealed the immunomodulatory effect, manifested itself in the change of the exudative-destructive type of inflammation to the proliferative-cellular [ 96 , 97 ].…”

“…According to the results obtained, at 24 h after MI the levels of interleukins in control group animals exceeded the norm for IL-1 by 8 times, for TNF by 7.8 times, for IL-6 by 2.5 times and for IL-10 in 4,3 times. Concurrently, in the animals of the experimental group with the compound L-17 administration, the increase in interleukin levels was significantly lower: IL-1 was increased 1.8 times, TNF-4.7-fold, IL-10–2.2-fold, and IL-6 level below the norm 2 times [ 97 ].…”

Dynamic Monitoring of Erythrocyte Distribution Width (RDW) and Platelet Distribution Width (PDW) in Treatment of Acute Myocardial Infarction

“…Because of the acute onset of AMI and early insensitivity of therapeutic effect evaluation, it is of great importance of identifying the early response in AMI [ 24 ]. At present, serum enzyme indicators are used, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and its isoenzymes [ 25 ]. However, AST and LDH are distributed in many organs of the body, and the diagnostic specificity is poor [ 26 ].…”