Gender Based Differences in Stress-induced Gastric Ulcer Formation and its Regulation by Nitric Oxide (NO): An Experimental Study.
2015
A variety of physiological and pharmacological factors are known to influence stress responses. Cold restraint
stress (CRS) induced gastric ulcerogenesis in both the sexes but such ulceration was found to be markedly
higher in male than in female rats. In males, CRS induced significant increases in both ulcer number and ulcer severity;
while the females though showed a trend towards increase in both the parameters, the extent of changes was
far less than in males. Pre-administration of the NO mimetic, L-Arginine (500 and 1000 mg/kg), prior to CRS, dose
dependently decreased ulcer number and severity in male rats. In female rats, L-Arginine also induced a gastric cytoprotective
effect during CRS but to a much lesser extent. On the other hand, inhibition of NO synthesis by LNAME
(25 and 50 mg/kg) further aggravated such stress ulcerogensis in both males and females, with aggravations
being more extensive in males. CRS induced ulcerogenesis was associated with reductions in levels of brain
and plasma NOx and GSH levels while MDA levels were elevated in both male and female rats- the magnitude of these changes being
higher in males than in females. In female rats, pretreatment with formestane (aromatase inhibitor) but not tamoxifen (estrogen receptor
blocker) aggravated stress ulcer formation as compared to vehicle treated CRS exposed rats. Formestane pretreatment also induced
greater suppressions in brain NOx and GSH and elevations in brain MDA, as compared to vehicle treated CRS rats. These results indicate
that estrogen and its interactions with oxidative stress markers and NO plays a key role in the gender based differences in stress induced
gastric ulcerogenesis. It may be speculated that, in males, CRS induces greater reductions in brain NO and enhancement in oxidative injury
resulting in greater severity of gastric ulceration. On the other hand, greater resistance of females to ulcerogenic effects of CRS may
be due to the protection conferred by estrogen and this effect seems to be related to interactions with brain NO.
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