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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2020; 66(5): 30-37


I.S. Fomenko1, Т.I. Bondarchuk1, A.S. Huet2, А.Ya. Sklyarov1

  1. Danylo Halytsky Lviv National Medical University, Ukraine
  2. Taras Shevchenko National University of Kyiv, Ukraine


The role of gaseous mediators NO and H2S and the cyclooxygenase/prostaglandins system in large intestinal mucosa was investigated in experiments on white rats under condition of experimental ulcerative colitis caused by introduction of acetic acid. Ulcerative colitis was accompanied by the formation of lesions of mucosal barrier of large intestine and the presence of ulcerative defects. The administration of H2S-releasing compound ATB-346 on the background of colitis significantly decreases the area of lesions as compared to naproxen or celecoxib action, that is the most probably caused by the action of H2S. Nonselective cyclooxygenase inhibition by naproxen was accompanied by the decrease of H2S concentration in blood serum and the level of gene Cbs expression in large intestinal mucosa, whereas under the condition of АТВ-346 action the above parameters were close to their normal values. Both naproxen and АТВ-346 decreased the level of gene Nos2 expression and activity of iNOS, which was sharply increased in colitis. Thus, the action of the naproxen derivative H2S releasing compound АТВ-346 is mainly caused by the action of hydrogen sulfide and its influence on іNOS system, and is manifested by a better cytoprotective effect as compared to naproxen action on the background of experimental ulcerative colitis.

Keywords: large intestinal mucosa; nitric oxide; hydrogen sulfide.


  1. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017;389(10080): 1756-70. CrossRef
  2. Martin AR, Villegas I, Alarcon de la Lastra C. The COX-2 inhibitor, rofecoxib, ameliorates dextran sulphate sodium induced colitis in mice. Inflamm Res. 2005;54(4): 145-51. CrossRef PubMed
  3. Sklyarov OYa, Panasyuk NB, Djura OR. Role of NOSsynthase system and lipid peroxidation processes in cytoprotective mechanisms under condition of ulcerative colitis. Exp Clin Physiol Biochem. 2009;1:38-44.
  4. Motta JP, Flannigan KL, Agbor TA, Beatty JK, Blackler RW, Workentine ML, Da Silva GJ, Wang R, Buret AG, Wallace JL. Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production. Inflamm Bowel Dis. 2015;21(5):1006-17. CrossRef PubMed
  5. Tsubota M, Kawabata A. Role of hydrogen sulfide, a gastransmitter, in colonic pain and inflammation. Yakugaku Zasshi. 2014;134(12):1245-52. CrossRef PubMed
  6. Myers BS, Martin JS, Dempsey DT, Parkman HP, Thomas RM, Ryan JP. Acute experimental colitis decreases colonic circular smooth muscle contractility in rats. Am J Physiol. 1997;273:928-36. CrossRef PubMed
  7. Sklyarov AYa, Panasyuk NB, Fomenko IS. Role of nitric oxide-synthase and cyclooxygenase/lipooxygenase systems in development of experimental ulcerative colitis. J Physiol Pharmacol. 2011;62(1):65-73.
  8. Sumbaev VV, Yasinskay IM. Influence of DDT on activity of nitric oxide synthase in the rats› liver, lungs and brain. Contemp Probl Toxicol. 2000;3:3-7.
  9. Kiselyk IO, Lutsyk MD, Shevchenko LYu. Peculiarities of nitrites and nitrates studies in peripheral blood of patients with viral hepatitis and syndrome of jaundice of different etiology. Lab Diagnost. 2001;3:43-5.
  10. Olkhovskiy OS, Zaichko N. Influence propargyl glycine and sodium content of hydrogen and H2S-indices of antioxidant system in the myocardium of rats of different ages. Med Chem. 2013;5(4):10-5.
  11. Sambrook J, Russell D. Molecular cloning: a laboratory manual. 3rd ed, Cold Spring Harbor Laboratory Pr; 2000.
  12. Konturek PC, Brzozowski T, Pierzchalski P, Kwiecien S, Pajdo R, Hahn EG, Konturek SJ. Activation of genes for spasmolytic peptide, transforming growth factor alpha and for cyclooxygenase COX-1 and COX-2 during gastric adaptation to aspirin damage in rats. Aliment Pharmacol Ther. 1998;12(8):767-77. CrossRef PubMed
  13. Moninuola OO, Milligan W, Lochhead P, Khalili H. Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of crohn's disease and ulcerative colitis exacerbation. Aliment Pharmacol Ther. 2018;47(11):1428-39. CrossRef PubMed PubMedCentral
  14. Flannigan KL, Agbor TA, Motta JP. Proresolution effects of hydrogen sulfide during colitis are mediated through hypoxia-inducible factor-1α. FASEB J. 2015;29(4):1591-1602. CrossRef PubMed
  15. Attene-Ramos MS, Wagner ED, Plewa MJ, Gaskins HR. Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res. 2006;4(1):9-14. CrossRef PubMed
  16. Rumi G, Tsubouchi R, Nishio H. Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats. J Physiol Pharmacol. 2004;55(4):823-36.
  17. Bir SC, Kolluru GK, McCarthy P, Shen X, Pardue S, Pattillo CB, Christopher GK. Hydrogen sulfide stimulates ischemic vascular remodeling through nitric oxide synthase and nitrite reduction activity regulating hypoxia-inducible factor-1α and vascular endothelial growth factor-dependent angiogenesis. J Am Heart Assoc. 2012;1(5):e004093. CrossRef PubMed PubMedCentral
  18. Polhemus DJ, Lefer DJ. Emergence of hydrogen sulfide as an endogenous gaseous signaling molecule in cardiovascular disease. Circ Res. 2014;114:730-7. CrossRef PubMed PubMedCentral
  19. Fomenko I, Sklyarov A, Denysenko N, Hrycevych N, Dranitsyna A, Wallace J. Interactions between nitric oxide and hydrogen sulfide generating systems in gastric mucosa under condition of the combined action of stress and NSAIDs. J App Pharm Sci. 2017;7(8):13-9.
  20. Thibault MP, Tremblay É, Wallace JL, Beaulieu JF. Effect of ketoprofen and ATB-352 on the immature human intestine: Identification of responders and non-responders. J Pediatr Gastroenterol Nutr. 2019;68(5):623-9. CrossRef PubMed PubMedCentral
  21. Shymans'ka TV, Hoshovs'ka Iu V, Semenikhina OM, Sahach VF. Effect of hydrogen sulfide on isolated rat heart reaction under volume load and ischemia-reperfusion. Fiziol Zh. 2012;58(6):57-66. CrossRef PubMed
  22. Strutynska NA, Korkach YuP, Mys LA, Luchkova AYu, Sagach VF. L-cysteine stimulates endogenous hydrogen sulfide synthesis, suppresses oxidative stress and mitochondrial permeability transition pore opening in the heart of old ratsFiziol Zh.2020;66(2-3):3-12. CrossRef
  23. Kumar M, Sandhir R. Hydrogen sulfide suppresses homocysteine-induced glial activation and inflammatory response. Nitric Oxide. 2019;90:15-28. CrossRef PubMed

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