In the dissertation the actual scientific problem of determining the role of metabolic, oxidative stress, apoptosis and necrosis of hepatocytes and changes in the structure of membranes of these cells and erythrocytes in the development of violations of the functional state of the liver during the prolonged action of block-copolymers based on oxypropylene and ethylene has been solved.
Theoretical generalization and solving the actual task of studying the structural and functional state of the liver of rats by determination of the activity of xenobiotic biotransformation processes, the activity of the oxidant antioxidant system, the activity of DNA repair, determination of morphological features of the liver under the conditions of action of block-copolymers, and the possibility of using the drug "Kvertin" for correction is substantiated for metabolic disorders in the body of rats. It was established that block-copolymers at doses of 1/10 and 1/100 of DL50 cause a violation of the structural and functional state of the liver, which is confirmed by an increase in the activity of transaminases, violation of sulfate and glucuronic conjugation. In an immunohistochemical study in hepatocyte nuclei of rats, an increase in the percentage of MGMT-labeled hepatocytes was determined in comparison with the control group.
Oxidative stress develops under the influence of block-copolymers on the basis of hydroxypropylene and ethylene in doses of 1/10 and 1/100 DL50 in the body of experimental animals: the content of 8-isoprostane, TBK-AP, DC increases in blood serum. There is a decrease in the activity of the antioxidant system: the activity of catalase, SOD of erythrocytes, blood glutathione peroxidase - by 42.69 %, 41.26 %, 32.37 % respectively, and the content of ceruloplasmin in the blood decreases by 47.24 % on average by 1/10 DL50 compared to control.
It has been determined that in the body of rats, toxicated with block-copolymers at a dose of 1/10 DL50, there is a violation of the state of cytoplasmic hepatocyte membranes: the externalization of phosphatidylserine in the phospholipid bile and the change in the fluorescence intensity of the probes on the erythrocyte membranes, the lack of changes in the field of glycerol and carbonyl groups of phospholipids, formation on the surface erythrocyte membranes of the extra shell.
It has been established that under the conditions of the study group xenobiotics for 45 days at a dose of 1/10 DL50 the hepatocytes survive by 18.21 %, activated by apoptotic hepatocytes, which is confirmed by an increase in the percentage of early-apoptotic hepatocytes (18.98 % on average) and late-apoptotic / necrotic cells ( an average of 9.75 %).
It was established that block-copolymers contribute to the development of hypoproteinemia due to hypoalbuminemia, uremia (the urea content increases by an average of 2,63 times); creatininemia (the creatinine content increased by 91.59 %). Reduced reproductive function of white rats is observed: hypotestosteronemia and hypoestrogenemia. Xenobiotics in doses of 1/10 and 1/100 DL50 cause a disruption of the carbohydrate metabolism: a decrease in the content of lactate, pyruvate in the background of hypoglycemia (glucose content decreased by 53.51 %, p <0.05). Hypoinsulinemia is detected, which may indicate a malformation of the functioning of the pancreas. The evaluation of lipid metabolism monitoring results under the influence of the studied group of xenobiotics at doses of 1/10 and 1/100 DL50 revealed hypercholesterolemia and an increase in the content of triglycerides.
The efficiency of using the drug "Kvertin" for correction of disorders of the structural and functional state of the liver of rats on the background of toxification with block-copolymers at a dose of 1/10 and 1/100 DL50 has been proved. At 45 days, the activity of AsAT, AlAT decreased by an average of 17 % and 19 %. "Kvertin" promotes the activation of biotransformation of, reduces the intensity of LPO processes and activates the antioxidant system, improves the monitoring parameters of the exchange of proteins, carbohydrates, lipids. On the basis of click-experimental studies, it has been proven that the drug "Kvertin" may be recommended for use in clinical practice by occupational physicians for correcting pathological changes in the structural and functional state of the liver due to the harmful effects of xenobiotics.
It was revealed that the leading links in the mechanism of biological action of block-copolymers are hepatotoxic, membranotropic, dysgomeostatic effects due to the development of oxidative stress.
