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

Keywords: water-immobilization stress, adrenaline-induced stress, gastric mucosa, nitrogen (II) oxide, hydrogen sulfide.


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.


Download data is not yet available.


Alhazzani, W., Alshahrani, M., Moayyedi, P., & Jaeschke, R. (2012). Stress ulcer prophylaxis in critically ill pa-tients:review of the evidence. Polskie Archiwum Medycyny Wewnętrznej, 122(3), 107–114. doi: 10.20452/pamw.1173.

Belostockij, N. I. (1988). Jazveobrazovanie v slizistoj obolochke zheludka krys pod vlijaniem katehola-minov. Patologicheskaja fiziologija i jeksperi-mental'naja medicina, 1, 24–27 (in Russian).

Bohdanova, O., Kuzmenko, L., Drobinska, O., & Ostap-chenko, L. (2007). Uchast systemy syntazy oksydu azotu v rozvytku ta vidnovlenni stres-indukovanykh urazhen slyzovoi obolonky shlunka. Visnyk Kyivsko-ho natsionalnoho universytetu imeni Tarasa Shevchenka, 12, 5–7 (in Ukrainian).

Bradley, P. P., Christensen, R. D., Rothstein, G. (1982). Cellular and extracellular myeloperoxidase in pyogen-ic inflammation. Blood, 60(3), 618–622. doi: 10.1182/blood.V60.3.618.618.

Brzozowski, T., Magierowska, K., Magierowski, M., Ptak-Belowska, A., Pajdo, R, Kwiecien, S., Olszanecki, R., & Korbut, R. (2017). Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Le-sions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Pep-tides. Curr Pharm Des., 23(27), 3910–3922. doi: 10.2174/1381612823666170220160222.

De Palma, G., Collins, S. M., Bercik, P., & Verdu, E. F. (2014). The Microbiota-Gut-Brain axis in gastrointes-tinal disorders: Stressed bugs, stressed brain or both? J. Physiol., 592(14), 2989–2997. doi: 10.1113/jphysiol.2014.273995.

Filaretova, L. Bagaeva, T., & Morozova, O. (2012). Stress and the stomach: corticotropin-releasing factor may protect the gastric mucosa in stress through involve-ment of glucocorticoids. Cell Mol Neurobiol., 32(5), 829–836. doi: 10.1007/s10571-012-9800-z.

Fomenko, I. S. (2015). Rol protsesiv lipoperoksydatsii u formuvanni vyrazkovykh ushkodzhen slyzovoi ob-olonky tovstoi kyshky shchuriv pry riznykh model-iakh stresu. Visnyk problem biolohii ta medytsyny, 1(3), 223–226 (in Ukrainian).

Fomenko, I., Bondarchuk, T., Emelyanenko, V., Denysenko, N., Pavlo, S., & Ilkiv, I. (2015). Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs. Current Issues in Pharmacy and Medical Sciences, 28(1), 37–41. doi: 10.1515/cipms-2015-0040.

Fomenko, I., Sklyarov, A., Denysenko, N., Hrycevych, N., Dranitsyna, A. (2017). Interactions between nitric oxide and hydrogen sulfide generating systems in gastric mucosa under condition of the combined action of stress and NSAIDs. J. Appl. Pharm. Sci., 7(8), 13–19. doi: 10.7324/JAPS.2017.70803.

Fomenko, I., Sklyarov, А., Bondarchuk, T., Biletska, L., Panasyuk, N., & Wallace, J.L. (2014). Efects Of Con-ventional And Hydrogen Sulfide-Releasing Nonsteroi-dal Anti-Inflammatory Drugs In Rats With Stress-Induced And Epinephrine-Induced Gastric Damage. Stress, 17(6), 528–537. doi: 10.3109/10253890.2014.967207.

Geyer, J. W., & Dabich, D. (1971). Rapid method for determination of arginase activity in tissue homoge-nates. Anal. Biochem., 39(2), 412–417. doi: 10.1016/0003-2697(71)90431-3.

Green, L. C., David, A. W. (1982). Analysis of nitrate, nitrite and (1515) nitrate in biological fluids. Anal. Bi-ochem., 126(1), 131–138. doi: 10.1016/0003-2697(82)90118-x.

Guo, Sh., Gao, Q., & Jiao, Q., Hao, W., Gao, X., & Cao, J. M. (2012). Gastric mucosal damage in water immer-sion stress: Mechanism and prevention with GHRP-6. World J. Gastroenterol., 18(24), 3145–3155. doi: 10.3748/wjg.v18.i24.3145.

Huerta-Franco, M. R., Vargas-Luna, M., Tienda, P., Del-gadillo-Holtfort, I., Balleza-Ordaz, M., & Flores-Hernandez, C. (2013). Effects of occupational stress on the gastrointestinal tract. World J Gastrointest. Pathophysiol., 4(4), 108–118. doi: 10.4291%2Fwjgp. v4.i4.108.

Kiselyk, I. O., Lutsyk, M. D., & Shevchenko, L. Iu. (2001). Osoblyvosti vyznachennia nitrativ ta nitrytiv v peryferychnii krovi u khvorykh na virusni hepatyty ta pry syndromi zhovtianytsi inshoi etiolohii. Laborator-na diahnostyka, 3, 43–45 (in Ukrainian).

Kudryavtsev, K. V., Markevich, A. O., Virchenko O. V. et al. (2014). Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile. Scientific World Jour-nal, 2014. article ID 217039. doi: 10.1155/2014/217039.

Magierowski, M., Magierowska, K., Kwiecien, S., & Brzozowski, T. (2015). Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing. Molecules, 20(5), 9099–9123. doi: 10.3390/molecules20059099.

Mönnikes, H., Tebbe, J. J., Hildebrandt, M. et al. (2001). Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointes-tinalmotility and sensitivity. Dig Dis., 19(3), 201–211. doi: 10.1159/000050681.

Ravaieva, M. Ju. (2012). Pol' oksida azota v realizacii mikrovaskuljarnyh jeffektov nizkointensivnogo mil-limetrovogo izluchenija. Uchenye zapiski Tav-richeskogo nacional'nogo universiteta im. V. I. Ver-nadskogo Serija “Biologija, himija”, 64(3), 165–170 (in Russian).

Takagi, K. Y., Kayuya, Y., & Watanabe, K. (1964). Stud-ies on drugs for peptic ulcer. A reliable method for producing stress ulcers in rats. Chem Pharm Bull., 12, 465–472. doi: 10.1248/cpb.12.465.

Wallace, J. L., Motta, J. P., & Buret, A. G. (2018). Hydro-gen sulfide: an agent of stability at the microbiome-mucosa interface. Am J Physiol Gastrointest Liver Physiol., 314(2), G143-G149. doi: 10.1152/ajpgi.00249.2017.

Wiley, J. W. (2007). The many faces of nitric oxide: cytotoxic, cytoprotective or both. Neurogastroenterol Motil., 19(7), 541 – 544.

Wilinski, B., Wilinski, J., Somogyi, E., Piotrowska, J., & Góralska, M. (2011). Digoxin increases hydrogen sul-fide concentration in brain, heart and kidney tissues in mice. Pharmacol. Rep., 63(5), 1243–1247. doi: 10.1016/s1734-1140(11)70645-4.

Abstract views: 79
PDF Downloads: 69
How to Cite
Motko, N., Fomenko, I., & Vozna, O. (2020). 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. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies. Series: Veterinary Sciences, 22(97), 88-94.