The role of gas mediators of nitrogen (II) oxide and hydrogen sulfide in the development of pathochemical changes in the mucous membrane of rats at water-immobilization and adrenaline-induced stress modeling

Abstract

Acute and prolonged psycho-emotional overstrain, i.e. stress, are the most frequent factors of ulcer formation in the digestive system. Therefore, the study of molecular mechanisms of stress impact is one of the most promising directions of modern experimental gastroenterology. However, the features of its molecular-biochemical action on the metabolic processes in the digestive system remain insufficiently studied. In this regard, we performed a comparative analysis of changes in indicators of systems of gas mediators of nitrogen (II) oxide and hydrogen sulfide synthesis at water-immobilization and adrenaline-induced stress modeling in experiments on white non-linear rats. Water-immobilization stress (WIS) was modelled by immobilizing animals in a plastic container, and adrenaline-induced stress (AIS) was modelled by injecting adrenaline at a dose of 2 mg/kg intraperitoneally. Modelling WIS caused formation of erosion and spot hemorrhage, located mainly along the folds of the fundus of the stomach. In this case, more noticeable changes were observed in the 5-hour WSI model. Injecting adrenaline at AIS model caused development of structural-hemorrhagic damage in the pyloric part and body of the stomach. The biochemical response to stress is complex, and the release of catecholamines is not the only case of stress. The synthesis of hormones such as glucagon, somatotropin and renin is activated. However, the most important role is played by cortisol, which level of growth in blood is measured to assess the degree of stress development. In our studies, changes in cortisol level in blood under different types of stress modeling (WIS and AIS) had their own peculiarities: at WIS conditions cortisol concentration increased sharply and remained high for 5 hours, while adrenaline did not cause the growth of this “stress hormone”. In our studies, in both models of stress-induced ulcerogenesis there were significant changes to the content of H2S and NO, that confirms the significant role of these substances in development and progression of ulcerogenesis in the digestive system. Thus, H2S concentration decreased at WIS and AIS. There is a significant increase in nitrogen oxide production in both WIS with different duration of action and AIS, which is caused by multiple activation of the inducible isoform of NO-synthase. Therefore, in experimental stress-induced ulcerogenesis, the metabolism of L-arginine in the mucous membrane of stomach is equally shifted towards the formation of NO, that under conditions of strengthening of free radical processes serves as a prerequisite for activation of oxidative-nitric processes and leads to the formation of structural-hemorrhagic damage to the surface of the mucous membrane of stomach. Our studies also show that ulcerative damage to the mucous membrane of stomach in all the types of studied stress was accompanied by an increase in myeloperoxidase activity, indicating an increase in permeability of hemocapillaries due to the development of the inflammatory process.