Study of the pleitropic effects of sodium 2-((4-phenyl-5- thiophen-3-ylmethyl)-1,2,4-triazol-3-yl)thio)ethanoate in conditions of experimental hyperlipidemia

Actuality.Atherosclerosis remains one of the leading global medical problems underlying most cardiovascular diseases, in particular coronary heart disease, hypertension, stroke, obliterating atherosclerosis of the lower extremities According to the World Health Organization, cardiovascular diseases are the leading cause of death in the world: they claim the lives of approximately 17.9 million people each year, accounting for about 32% of all deaths.Of these, more than 85% are caused by myocardial infarctions and strokes, most of which develop against the background of atherosclerotic vascular changes.In developed countries, atherosclerosis occurs in more than 50% of men and about 40% of women over the age of 50, and this trend continues despite advances in prevention and treatment.In Ukraine, according to official data of the Ministry of health, cardiovascular diseases account for more than 65% of the mortality structure, and the number of complications caused by atherosclerosis is growing every year.In this regard, an in-depth study of the mechanisms of atherosclerosis development and the identification of sensitive biomarkers that allow not only early detection of pathological changes, but also accurate prediction of the risk of complications is extremely important.Of particular value are so -called pleiotropic biomarkers-molecules that simultaneously reflect several key pathophysiological processes, such as inflammation (CRP), activation of the hemostatic system (D-dimer), ischemic myocardial damage (MV-CPK) and the functional state of the endothelium (eNOS).In this context, given the significant hypocholesterolemic and hypotriglyceridemic effects found in the "leader compound", as well as the ability to increase the level of high-density lipoprotein cholesterol (HDL cholesterol), it is of obvious scientific interest to study the potential pleiotropic effects of sodium 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio)ethanoate under experimental hyperlipidemia.In particular, the study of its effect on key biomarkers of inflammation, coagulation state, ischemic myocardial injury and endothelial function can reveal new mechanisms of action of the compound and the potential for its use as a drug for the treatment of atherosclerosis.The aim of the study is to study the effect of sodium 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio)ethanoate compound on pleiotropic biomarkers under experimental hyperlipidemia. . 2, 2025. Education and Science No. 249 of 01.03.2012.Experimental hyperlipidemia was modeled by administration of cholesterol and ergocalciferol for 5 days.Serum levels of eNOS (enzyme immunoassay), CRP, MV-CPK, and D-dimer (ACCENT-200 biochemical analyzer, corresponding reagents produced by Cloud-Clone, Cormay, and Vector-best) were determined. Materials and methods. The study of the biological activity of sodium salt 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio) ethanoic acid was conducted on 20 white nonlinear rats weighing 160-310 g, obtained from the nursery of the Institute of Pharmacology and toxicology of the National Academy of Medical Sciences of Ukraine. Experiments were performed on the basis of a certified vivarium and the Department of Clinical Pharmacy, Pharmacotherapy, Pharmacognosy and Pharmaceutical chemistry of Zaporizhia State Medical and Pharmaceutical University. The animals were kept under standard conditions in accordance with the requirements of EU directive 2010/63/ EC and order of the Ministry ofResults.In the experimental hyperlipidemia model, a decrease in eNOS levels and an increase in CRP, D-dimer, and MV-CPK in rat blood serum were observed, which indicated endothelial dysfunction, inflammation, activation of the hemostatic system, reduction of ischemic myocardial damage, and thrombotic processes.Administration of sodium 2- ((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio) ethanoate significantly increased eNOS activity (by 236.46%), exceeding the effect of atorvastatin and improving the functional state of the endothelium.The level of D-dimer when using the test compound decreased by 34.39%, which was more effective compared to atorvastatin and indicated a decrease in the activation of the hemostatic system.A significant decrease in MV-CPK activity and CRP levels was also recorded, which confirms reduction in ischemic myocardial damage and anti-inflammatory properties of the compound.Thus, the studied compound shows pronounced pleiotropic effects, in particular, endothelioprotective, antithrombotic, metabolitotropic and anti-inflammatory.Conclusions.The sodium compound 2-((4-phenyl-5-(thiophene-3-ylmethyl)-1,2,4-triazole-3-yl)thio)ethanoate exhibits pronounced endothelioprotective and antithrombotic activity, which was confirmed by an increase in eNOS levels and a decrease in the D-dimer.Its anti-inflammatory and reduces ischemic myocardial damage have been established.The studied compound was not inferior in strength of pharmacodynamic effects to the reference drug atorvastatin.