Fomenko I. Systems of nitric oxide and hydrogen sulphide in mechanisms of ulcerogenesis in mucosa stomach and large intestine

The thesis is devoted to the study of molecular and biochemical mechanisms of relationship between metabolism of gas mediators NO та H2S in gastric and colonic mucosa under condition of the stress-induced ulcerogenesis and the influence of cyclooxygenase and lipoxygenase inhibitors. Experiments conducted on white rats allowed us to ascertain that H2S, released from compounds АТВ-346 and Les-5054 actively influences NO-synthase parameters (level of NO stabile metabolites, gene expression and activity of NO-sythases). This explains biochemical mechanisms of relationship between NO and H2S. It was proved that non-selective COX inhibition under condition of water restrain stress is accompanied by the considerable decrease of Nos2 gene expression and iNOS activity. On one hand it can play a role of a biochemical basis of the ulcerogenesis potentiation in gastric mucosa, on the other hand it proves the presence of relationships between systems COX/PGs and NOS/NO and their crucial role in the formation of gastric mucosal destructive lesions. It was shown that the combined action of stress and nonsteroidal anti-inflammatory drugs (NSAIDs) doesn't cause visible macroscopic changes in colonic mucosa, however the activation of lipid peroxidation, the development of oxidative stress, the decrease of Cbs gene expression and H2S took place.