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.
NSAIDs, stress, nitric oxide, gastric mucosa.
- Alejnikova TL, Rubtsova GV, Pavlova NA. Manuals for practical lessons in biochemistry. Moscow: Medicine; 1988:239 p.
- Sklyarov AYa, Fomenko IS. Nonsteroidal anti-inflammatory drugs, mechanisms of their action, peculiarities of use. Practical medicine. 2007; 14(3): 123-132.
- 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.
- 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.
- Bhatia V, Tandon RK. Stress and the gastrointestinal tract. Journal of gastroenterology and hepatology. 2005; 20: 332-339.
- 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.
- Geyer JW, Dabich D. Rapid method for determination of arginase activity in tissue homogenates. Anal. Biochem. 1971; 39(2): 412-417.
- 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.
- Lanas A. Role of nitric oxide in the gastrointestinal tract. Arthritis Research & Therapy. 2008; 10 (2): 4.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Wallace JL, Dicay M, McKnight W, Martin GM. Hydrogen sulfide enhances ulcer healing in rats. The FASEB Journal. 2007; 21: 4070-4076.