Доклиническое изучение антиатеросклеротического препарата фирутас на патоморфологические изменения органов животных при длительном введении

Аннотация

This article is devoted to the preclinical study of the anti- atherosclerotic drug firutas on pathomorphological changes in animal organs during prolonged administration. Preclinical study of the general toxicology of the drug "Firutas" showed that it belongs to the IV class of low-toxic compounds. The drug "Firutas" does not have a cumulative and locally irritating effect. With repeated intramuscular administration to mice and rats, it does not affect the behavior and weight dynamics of animals, does not have a toxic effect on the composition of peripheral blood, kidney and liver function, as well as on the pathomorphology of animal organs and tissues. All the above data allow us to conclude that the drug does not have a toxic effect on the body of animals. 1 Relevance Atherosclerosis is a chronic lesion of the arteries caused by the proliferation of multiple dense nodular thickenings of the walls of the artery (plaques), narrowing its lumen and contributing to the formation of a blood clot, a thrombus, which can clog the vessel. Atherosclerosis develops as a result of complex structural changes occurring in the intima (inner layer) and in the media (muscle layer) of the arteries, and it is associated with the accumulation of lipids and mucopolysaccharides in the blood vessels, the proliferation of connective tissue and the deposition of calcium. Cardiovascular disease, and this ischemic heart and brain disease, occlusive peripheral arterial disease, is the most common cause of morbidity, mortality and disability in the population of industrially developed countries [1,2,3,12]. Cardiovascular disease is the leading cause of death in the world. About 1/3 of the total number of deaths is due to this cause (17.9 million people per year). The most important modifiable risk factors for cardiovascular disease are hypertension, overweight and dyslipoproteinemia. Arterial hypertension is widespread among the Corresponding author: shahida63@inbox.ru Ф^ЯЙ1£ФЛЙ^^2021^13ЛЖ39^Ж13ЙСЫП J Ind Hyg Occup Dis , 2021 , Vol.39 , No.13 population (approximately 40% in the world) and causes about 9.4 million deaths per year 77 [5,6,7]. It is known that dyslipoproteinemias, in particular an increased level of total cholesterol and low-density lipoproteins, increase the risk of developing cardiovascular diseases and cardiovascular mortality [4,5,6,8,18]. At the same time, hypertriliciridemia has remained an ambiguous risk factor for cardiovascular diseases for many years. However, recently there has been information about the presence of an independent negative effect of an increased level of triglycerides on the development of diseases of the cardiovascular system [9,10]. And since hypertriglyceridemia is highly common (30% of the population in the United States, 29.2% in Russia), it can be assumed that it makes a significant contribution to the formation of the population risk of mortality [9, 10, 11]. Treatment of atherosclerosis is one of the urgent problems of modern medicine. Currently, for the prevention and treatment of atherosclerosis, there are a number of drugs belonging to different groups. However, with their long-term use, they cause a number of adverse side effects. In this regard, the search and study of new, more effective, less toxic hypolipidemic and antiatherosclerotic drugs is an urgent problem of modern pharmacology. Earlier, we found that the drug Firutas has a pronounced hypolipidemic, antiatherosclerotic effect and surpasses nicotinic acid in activity [1,3,4,5]. 2 The purpose of preclinical study Toxicological studies of the drug "Firutas" is to establish the nature and severity of its damaging effect on the body of experimental animals and assess its safety. 3 Research materials and methods The general effect and toxicity of firutas was studied on white mice (weighing 18-20 g) and on rats (180-200 g) with oral and intra-abdominal administration at doses of 100, 500, 1000, 2000 and 3000 mg / kg 1-5% solution of the drug. To study the chronic toxicity of firtas, rats with an initial weight of 120-170 g were used. The experiments were carried out in the winter- spring season (December-May). The animals were divided into 3 groups. The drug was administered daily (7 times a week) orally for 180 days at doses of 100 mg / kg (therapeutic dose), 500 mg / kg (5 times higher than the therapeutic dose). The third group served as a control, where distilled water was introduced under similar conditions. After the end of the experiment, rats of all groups were decapitated and sent for dissection and pathomorphological examination of internal organs [4,12,18]. During the experiment (in the initial state and after the completion of the experiment), the following was noted: the general condition was assessed by daily examination of the animals, the dynamics of body weight was weighed once a month, the behavior of rats was assessed by motor activity. All animals were subject to pathological examination at the end of the st