الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
CO has been found to be produced in every living cell in a biochemical reaction catalyzed by HO which degrades heme into biliverdin, CO and iron. Endogenous CO is not a waste product, but acts as a chemical messenger mediating and modulating many intracellular biochemical reactions that regulate physiological functions. Apart from the generalized smooth muscle relaxant effect CO produces in nearly all systems including the gastrointestinal system, its effect on gastric secretion and mucosal protection has not been yet studied under different conditions. So the present work is a trial to evaluate the role of CO in the pathophysiologic mechanisms of experimentally induced gastric ulceration caused by cold restraint-stress and indomethacin administration. The drugs selected for this investigation included: Hemin, SnCl2 (HO inducers) and ZnPP (HO inhibitor). The adult male albino rats were then randomly classified to the following groups: control, CRS and IND-treated groups and the same groups treated with: hemin (25 mg/kg, i.p. 4 times/week for 4 weeks), SnCl2 (10 mg/100 g, s.c. twice a week for 5 weeks) and ZnPP (50 µmol/kg/d, s.c. for 10 days). Three hours after pyloric ligation, the rats were anesthetized by light ether anesthesia. Then rats were decapitated, their stomachs were removed, opened along the greater curvature and the gastric content of each stomach was collected for determination of volume, free and total acid outputs, mucin concentration and pepsin activity. Each stomach was rinsed in ice-cold saline, washed with IND (10 g/ml) and scored for macroscopic gross mucosal lesions by two independent observers unaware of the treatment given using a binocular magnifying lens. The gastric mucosa was then scraped over ice and stored at -20OC till used for assessment of gastric mucosal lipid peroxide, HO-1, PGE2 and NO. Current results demonstrated that the pathogenesis of gastric ulcer appears to be multifactorial depending on protective and aggressive factors. CO is a double faced gasotransmitter as it counteracts the aggressive factors and also some of the protective factors and the dominant is the final result found in this study. The net effect, CO has a gastroprotective effect inspite of decreasing the protective PGE2 and NO. CO was also reported to have anti-inflammatory and anti-apoptotic effects. In conclusion, CO plays an important regulatory role in maintaining gastric mucosal integrity. The protective effects of CO appears to be multifactorial including, inhibition of gastric secretion, decrease proteolytic activity and attenuation of lipid peroxidation inspite of marked decrease in NO and PGE2 levels. Therefore, the potential use of various HO inducers could be a beneficial role in protecting against various mucosal injuries and the controversial effects ZnPP on either CRS or IND induced gastric ulcers could be attributed to the presence of zinc which is known to have a protective anti-ulcer effect. This may shed light on the importance of excluding zinc preparations in all studies dealing with gastric ulcers and opens the way for further research concerning the dose response effects of HO inhibitor on the pathogenesis of different models of gastric ulcer.