Among the factors that could cause structural and functional changes of the small intestine is stress and the effect of cyclooxygenase blockage. There are links between COX / prostaglandin and NOS/NO systems: NO can directly stimulate the expression of COX and biosynthesis of prostaglandin, while COX and prostaglandin are involved in regulation of NOS activity. The purpose of our study was to investigate changes of NO-synthase, arginase and processes of lipid peroxidation activity under conditions simultaneous of COX-1/COX-2/5-LOX blockage in the small intestine mucosa in stress.
Studies were conducted on 48 white rats weighing 180–250 g according to the ethical requirements under the provision of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. Animals were in a vivarium under certain lighting conditions, temperature and a standard diet. They had free access to water for 20 hours before investigation.
Animals were divided into 5 groups: 1) control (n=8); 2) animals with the modeling of water-immobilization stress (WIS) by immobilizing in a plastic container and immersed vertically in water (23±0,5°C) to the level of the xiphoid appendix during 5 hours; 3) animals administered nonselective blockers of COX naproxen a single dose 10 mgkg–1 per os 30 minutes before modeling WIS; 4) animals administered selective blockers of COX- 2 celecoxib a single dose 10 mgkg–1 per os 30 minutes before modeling WIS; 5) animals administered COX-2/5-LOX inhibitor 2-amino-5-(3,5-di tert butyl-4-hydroxy benzylidene)- thiazol-4-one (2A5DHT) a single dose 10 mgkg–1 per os 30 minutes before modeling WIS. In homogenates of the small intestine mucosa was measured activity of NO-synthase; content of nitrite anion using Griss reagent, arginase activity, the content of TBA-active products. Statistical analysis of the experimental results was performed using the application ANOVA „Statistica”.
Under the conditions of WIS during 5 hours the activity of iNOS increased almost 3 fold at that the cNOS and arginase activity decrease (for 51% and 31%, р<0,05, respectively); the content of TBA-active products rose for 19% (р<0,05 respectively), as evidenced by the activation of oxidative metabolism of L-arginine, iNOS, and activation of lipoperoxidation processes.
Inhibition of COX-1/COX-2 by naproxen under the WIS leads to a decrease of iNOS activity for 38% (p<0,05), at thet arginase activity did not change, cNOS activity tended to increase (12,5%), the content of TBA-active products and nitrite anion was not significantly changed as compared with indexes in WIS.
Effects of selective COX-2 blocker celecoxib under the WIS did not cause significant changes of iNOS, the content of TBA-active products, nitrite anione, the activity of cNOS and arginase.
The WIS during 5 hours was accompanied by the considerable increase of iNOS activity and the rise of lipoperoxidation processes intensity in the mucosa of small intestine while the arginase and cNOS activity decreased. Inhibition of COX-1/COX-2 by naproxen in WIS leads to a decrease of iNOS activity in the small mucosa intestine as compared with indexes in WIS. Inhibition of COX-2 activity as well as COX-2/5-LOX in WIS during 5 hours the mucosa of small intestine did not cause marked changes in the activity of iNOS and arginase as compared with indexes WIS.
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