Українська English

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. 2014; 60(2): 51-56

Parameters of NO synthase system of gastric mucosa in rats under stress conditions and inhibition of cyclooxygenase

Fomenko IS, Bondarchuk TI, Bilets'ka LP, Panasiuk NB, Skliarov OIa

    D. Halytskyi National Medical University, Lviv, Ukraine


In experiments on rats with modeled water-restrained stress, the influence of nonsteroidal anti-inflammatory drugs of different genesis on morphological status of gastric mucosa and changes of NO-synthase system parameters have been studied Administration of nonselective cyclooxygenese inhibitor naproxen in the water-restrained stress model in rats potentiated the increase of severity of damage of gastric mucosa. At the same time, the activity of both inducible and constitutive isoforms of NO-sythase decreased. The parameters of lipoperoxidation remained at the level observed during water-restrained stress. It was shown the advantages of the use of H2S-releasinfg nonsteroidal anti-inflammatory drug ATB-346, which are associated with its cytoprotective effect of the drug manifested by a decreased total area of gastric damage. However, parameters of lipoperoxidation and NOsyntase system did not differ substantially from those in the group treated with napoxen, indicating the prevalence of parent molecule (naproxen) in regulation of function of NO-system Administration of dual COX/LOX inhibitor, the compound 2A5DHT, caused a decrease of gastric damage as compared to the effect of naproxen. The activity of iNOS remained much higher than under condition of the naproxen action.

Keywords: NSAIDs, stress, nitric oxide, gastric mucosa.


  1. Alejnikova TL, Rubtsova GV, Pavlova NA. Manuals for practical lessons in biochemistry. Moscow: Medicine; 1988:239 p.
  3. Sklyarov AYa, Fomenko IS. Nonsteroidal anti-inflammatory drugs, mechanisms of their action, peculiarities of use. Practical medicine. 2007; 14(3): 123-132.
  5. Sumbajev VV, Jasinskaja IM. The influence of DDT on the activity of nitric oxide synthase in liver, lungs and brain of rats. Modern problems of toxicology. 2000: 3: 3-7.
  7. Timirbulatov RA, Seleznev EI. Method for increasing the intensity of free radical oxidation of lipid-containing components of the blood and its diagnostic significance. Lab. Delo. 1981; 4: 209-117.
  9. Bhatia V, Tandon RK. Stress and the gastrointestinal tract. Journal of gastroenterology and hepatology. 2005; 20: 332-339. CrossRef PubMed
  11. Coruzzi G, Venturi N, Spaggiari S. Gastrointestinal safety of novel nonsteroidal antiinflammatory drugs: selective COX-2 inhibitors and beyond. ACTA BIOMED. 2007;78: 96-110. PubMed
  13. Geyer JW, Dabich D. Rapid method for determination of arginase activity in tissue homogenates. Anal. Biochem. 1971; 39(2): 412-417. CrossRef  
  14. Kwiecien S, Konturek PC, Sliwowski Z, Mitis-Musiol M, Pawlik MW, Brzozowski B, at all. Interaction between selective cyclooxygenase inhibitors and capsaicin sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress. J. Physiol. Pharmacol. 2012; 63(2): 143-151. PubMed
  16. Lanas A. Role of nitric oxide in the gastrointestinal tract. Arthritis Research & Therapy. 2008; 10 (2): 4. CrossRef PubMed PubMedCentral
  18. Liu L, Cui J, Song Ch-J, Bian J-S, Sparatore A, Del Soldato P, Wang X-Yu, Yan Ch-D. H2S-Releasing Aspirin Protects against Aspirin-Induced Gastric Injury via Reducing Oxidative Stress. PLOS ONE. 2012; 7(9): 46301. CrossRef PubMed PubMedCentral
  20. Martel-Pelletier J, Lajeunesse D, Reboul P.Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis. 2003; 62: 501-509. CrossRef PubMed PubMedCentral
  22. Mollace V, Muscoli C, Masini E et al. Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors. Pharmacol. Rev. 2005; 57: 217-252. CrossRef PubMed
  24. Nasadyuk C, Sklyarov A. Thymohexin exhibits cytoprotective effect in experimental gastric lesions in rats both through the inhibition of inducible nitric oxide synthase and reduction of oxidative mucosal damage. Regulatory Peptides. 2013; 180: 50-57. CrossRef PubMed
  26. Takagi KY, Kayuya Y, Watanabe K. Studies on drugs for peptic ulcer. A reliable method for producing stress ulcers in rats. Chem Pharm Bull. 1964; 12: 465-472. CrossRef PubMed
  28. Wallace JL, Caliendo G, Santagada V, Cirino G. Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346). British Journal of pharmacology. 2010; 159: 1236-1246. CrossRef PubMed PubMedCentral
  30. Wallace JL, Dicay M, McKnight W, Martin GM. Hydrogen sulfide enhances ulcer healing in rats. The FASEB Journal. 2007; 21: 4070-4076. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.