Kondro M. The meсhanіsms of the hepatіс steatosіs development іn the event of a vіsсeral obesіty of varіous orіgіn and іts adjustment

Object of the research: the mechanisms of the diet- and glutamate-induced hepatic steatosis development in the event of visceral obesity and its correction. Aim: to determine the mechanisms of the hepatic steatosis development in the event of visceral obesity, induced by a high-calorie diet and neonatal injection of sodium glutamate, and to assess the preventive influence of the multi-probiotic Symbiter acidophilic concentrated and prebiotic nanocrystalline cerium dioxide on hepatic steatosis development. Methods of the investigation and equipment: physiological, biochemical, molecular, biophysical, immunochemical, histomorphological and morphometric methods, methods of mathematical statistics. Theoretical and practical results: the obtained scientific results expand and generalize modern ideas about the mechanisms of development of steatohepatosis of different genesis and under conditions of correction. This makes it possible to recommend preclinical studies of the pharmacokinetics and pharmacodynamics of nanocrystalline cerium dioxide aimed at the development of a new drug for prevention of hepatic steatosis, induced by various etiological factors. The results of the experimental studies of the corrective influence mechanisms of the multi-probiotic Symbiter acidophilic concentrated provide grounds for its more extensive use in patients with non-alcoholic fatty liver disease and those under the risk of its development. Novelty: it has been first determined that the rats with glutamate-induced hepatic steatosis suffer from impaired functioning of serotonergic system in brain tissue, blood serum and duodenum. It has been demonstrated that in rats under a long-term high-calorie diet or after neonatal injection of sodium glutamate the hepatic steatosis development associated with mitochondrial dysfunction, characterized by changes in the lipid composition of the inner mitochondrial membrane of hepatocytes, increased oxygenated products, changes in the enzymatic activity of all components of electron transport chain, which was successfully corrected by regular administration of multi-probiotic or nanocrystalline cerium dioxide. It has been first determined that the splenic mass and number of splenocytes in rats with diet- and glutamate-induced hepatic steatosis is reduced, which triggers the immune system dysfunction, namely the dysbalance of pro- and anti-inflammatory cytokines content in blood serum. The data on the significant increase of the levels of mRNA expression of Tgfb1, Ptgs2 and Hgf genes in the rats’ hepatocytes in case of glutamate-induced hepatic steatosis has been received, which evidences the development of fibrosis and inflammatory process in the liver. The tested parameters significantly improved secondary to regular administration of the multi-probiotic or nanocrystalline cerium dioxide in rats with glutamate-induced hepatic steatosis. The degree of implementation: the utility model patent and 2 certificates of technical innovation were obtained based on the thesis findings. The thesis findings have been integrated into the educational process and scientific activities of the departments of Danylo Halytsky Lviv National Medical University, Ivano-Frankivsk National Medical University, Bukovinian State Medical University, I.Ya. Horbachevsky Ternopil National Medical University, Ukrainian Medical Stomatological Academy and Taras Shevchenko Kyiv National University. The multi-probiotic Symbiter acidophilic concentrated has been implemented as a preventive medicine for hepatic steatosis into the treatment process at Municipal Non-Profit Enterprise of Lviv Regional Council MNE LRC Lviv Regional Clinical Hospital, MNE LRC Lviv Regional Children’s Clinical Hospital Okhmatdyt and MNE LRC Lviv Regional Infectious Clinical Hospital. Areas of application: medicine.