Rytsyk O. Mechanisms of development of nitrosoxidative stress in the conditions of experimental carcinogenesis, ways of its prevention and correction

The dissertation is devoted to the study of metabolic disorders in experimental rats during modeling of carcinogenesis of the colon, as well as to the experimental substantiation of the previous use of the antioxidant resveratrol in order to facilitate the course of experimental carcinogenesis. The activity of the NO-synthase system in the conditions of induced carcinogenesis and its relationship with oxidative processes was studied for the first time. The indicators of the antioxidant system, in particular its enzymatic and non-enzymatic components, were studied on the model of dimethylhydrazine-induced carcinogenesis, and markers of cytolysis were studied. It has been established that oxidation processes are activated during DMH-induced carcinogenesis, which is indicated by an increase in serum content of TBA-active products in 6.0 times and 4.3 times 2,4-dinitrophenylhydrazones of neutral and 2.5 times basic character after 30 weeks of cancer development. In addition, there was a disturbance in the functioning of the NO system, which is confirmed by an increase in nitrite ion, activation of inducible NO synthase and inhibition of endothelial NO synthase activity in rat serum in the last period of the study (7 months from the start of the experiment). It was substantiated the possibility of prophylactic use of resveratrol to reduce the manifestations of metabolic disorders in the dynamics of colon adenocarcinoma in order to activate the body’s antioxidant defense system, normalize free radical oxidation processes and slow down cytolysis. It was established that the antioxidant resveratrol promotes the development of oxidative and nitrooxidative stress under conditions of experimental cancerogenesis in animals. In animals treated with resveratrol, the activity of inducible NO synthase was inhibited (1.8 times in serum and 1.9 times in the liver) and the activity of its endothelial form was restored. It is proved that this tool leads to the restoration of the antioxidant defense system in rats, as indicated by the increase superoxide dismutase (1.9 times) and catalase activity (2.1 times) in the serum in the final development of adenocarcinoma. It was found that resveratrol has moderate membrane-protective properties, which led to a decrease in the serum of animals with carcinogenesis of the activity of membrane-dependent aminotransferases, gamma-glutamyltraspeptidase and alkaline phosphatase. Used for prophylactic purposes for the first time, resveratrol reduced the degree of endogenous intoxication, which is indicated by a decrease in the content of medium weight molecules in the serum of dimethylhydrazine-affected rats, restoration of erythrocyte membrane permeability and decrease in urea content. On the model of experimental carcinogenesis the antioxidant and membrane-protective properties of resveratrol, which is used for prophylactic purposes to facilitate the oncological process, were confirmed.