No 1 (2021)

The paper presents the results of an experimental study of the dose-dependent nature of functional changes in the body systems under chronic administration of uranyl acetate dihydrate in doses of 0.5 and 5.0 mg/kg per element for 18 weeks. The study was performed on 45 male outbred rats. It has been shown that uranyl acetate dihydrate in a dose of 0.5 mg/kg had no significant effect on hematological parameters. At the same time, activation of bactericidal activity of neutrophils, a decrease in the immunoregulatory index, and an increase in the blood concentration of tumor necrosis factor (TNF-α) have been revealed. The toxicant administered to rats in a dose of 5 mg/kg led to a decrease in the absolute number of erythrocytes, hemoglobin, hematocrit, platelets, the release of myelocytes into the blood, basophilia, monocytosis, the appearance of leukolysis cells and plasmatization of lymphocytes. On the part of the immune system, an increase in the biocidal capacity of neutrophilic granulocytes, TNF-α production, an increase in the number of CD8+ cells, and a reduction in the CD4+/CD8+ ratio have been found. Uranyl acetate dihydrate had a dose-dependent effect only on the number of cytotoxic T-lymphocytes, T-cells with the CD4+CD8+ phenotype, on the immunoregulatory index, and on the level of TNF-α. Hyperglycemia and glucosuria were also dose-dependent. An increase in glucose in the blood and urine indicated a violation of carbohydrate metabolism and kidney function. There was a decrease in the concentration of thyroxine, testosterone and an increase in the level of insulin. Uranyl acetate dihydrate led to the development of insulin resistance. The level of hormones did not depend on the dose of the toxicant administered to the animals.

Immune disorders arising from liver damage of various origins and the mechanisms of their development are still poorly understood. The functions of the immune system are carried out against the background of metabolic processes and their shifts caused by the action of various agents on the body, as well as liver cells - hepatocytes. Typical metabolic changes that occur when the liver is affected by various toxic factors are combined with certain features of metabolic disorders in certain organs and tissues, due to the specifics of their structural and functional organization, the nature of the inducing agent and the primary link of its effect on cells and the body as a whole. The relationship of numerous metabolic changes, violations of the functional activity of hepatocytes arising in such a pathology with the dysfunction of the immune system has not yet been sufficiently studied, as well as the most effective methods of correction have not been established. Currently, the issues of pathogenesis, diagnosis and treatment of acute liver diseases remain among the most relevant in medicine, both due to the complexity of diagnosis and the choice of optimal treatment methods, and the tendency towards an increase in the number of patients with these diseases. The emergence and development of cellular technologies have created serious scientific prerequisites in this area.

The paper presents the results of studying the toxicological profile of a new pharmaceutical substance RU891 with antithrombogenic properties. The minimum toxic dose (TDmin) for RU-891 by peroral administration is 230 mg/kg < TDmin ≤ 460 mg/kg. In experiments on the acute toxicity of the compound RU-891, the nature and severity of its damaging effect on the body of experimental animals were established and the safety of its action was evaluated. When studying the toxic effect of the test sample, the tolerated and toxic doses of RU-891 were determined, and the most sensitive organs and systems of the body were identified.