Gastric Mucosal Protective Action of Nicorandil against Gastric Lesions Induced by Indomethacin

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.