Gastric Mucosal Protective Action of Nicorandil against Gastric Lesions Induced by Indomethacin | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 6, Volume 28, Issue 1, June 2008, Page 59-76 PDF (206.09 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2008.36836 | ||||
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| Authors | ||||
| Selim Abdel-Hakim* 1; Salama Abdel-Raheem2 | ||||
| 1Department of Physiology , Faculty of Medicine, El-Minia University | ||||
| 2Department of Biochemistry, Faculty of Medicine, El-Minia University | ||||
| Abstract | ||||
| The present investigation was an attempt to evaluate the anti-ulcer activity of nicorandil in indomethacin-induced ulcer model. The drugs selected in that investigation included: nicorandil (KATPchannel opener), glabinclamide (KATP channel blocker), cimetidine and indomethacin. Male albino rats weighing 150-200 grams were fasted for 24 hours prior to the experiment. Pyloric ligation was performed 2 hours after indomethacin administration. Rats were randomly divided into the following groups of 10 rats each: Control (C)group, non pretraeted indomethacin (I)group, cimetidine pre-treated(CI), tween 80 pre-treated(TI), glibenclamide pretreated(GI), nicorandil pre-treated(NI)and nicorandil + glibencalamid pre-treated(NGI) indomethacin groups. After 5 hours from indomethacin administration (and 3 hours from pyloric ligation), rats were sacrificed. Their stomachs were removed, opened along the greater curvature and the gastric contents were collected for analysis of gastric juice parameters (volume, pH, total and free acid concentration, pepsin concentration and mucin concentration). The stomachs were washed with ice-cold saline and scored for macroscopic gross mucosal lesions. The stomachs were washed with indomethacin and stored at -80 o C until used for assessment of gastric mucosal lipid peroxides, histamine, PGE2and nitrites. Results: Ulcerative lesions were observed in indomethacin treated rats where the ulcer index (UI) mounted to 18.1 ± 1.04. Nicorandil significantly protected rats against gastric ulceration. Indomethacin insignificantly altered gastric juice volume, pH, total and free acid concentration, pepsin and mucin concentration. Cimetidine significantly protected rats from gastric mucosal ulceration, and significantly reduced gastric juice volume. Pretreatment with glibenclamide did not alter gastric lesion UI while it significantly increased gastricjuice volume, free and total acid concentration. Co-administration of glibenclamide with nicorandil significantly decreased gastric juice pH and mucin concentration and significantly increased gastric juice volume, free and total acid concentration. The increase in gastric mucosal histamine and nitrite contents observed with nicorandil was not affected by co admistration of glibenclamide with it.Conclusion:nicorandil significantly protected gastric mucosa from indomethacin-induced lesion. The mechanism underlying that protection involves mainly KATPchannel opening, leading to decreased gastric acid secretion and proteolytic activity, NO donation, reduction of lipid peroxidation and normalization of the detrimental elevation of gastric mucosal nitrites level. Histamine and PGE2do not seem to contribute to nicorandil’s gastroprotective effects. | ||||
| Keywords | ||||
| Nicorandil; gastric mucosa; Indomethacin; cimetidine; Glibenclamide; ulcer index | ||||
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