Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rat

Background and Aims: In the gastric mucosa of portal hypertensive rats, adaptive cytoprotection against ethanol-induced damage is impaired. The aim of this study was to determine relation between impaired adaptive cytoprotection and oxidative stress. Methods: Portal hypertension was produced in male Sprague-Dawley rats by inducing staged portal vein occlusion. Oxidative stress levels were evaluated by measuring malondialdehyde and nitrotyrosine levels in the rat gastric mucosa with or without 10% ethanol pretreatment. Inhibition of oxidative stress by an anti-oxidant agent was estimated, and glutathione levels were also measured. Adaptive cytoprotection to 70% ethanol treatment was evaluated by measuring the gastric mucosal injury index in the presence or absence of the anti-oxidant. Results: The portal hypertensive gastric mucosa pretreated with 10% ethanol had significantly higher oxidative stress levels than the mucosa not pretreated with 10% ethanol. However, the sham-operated gastric mucosa pretreated with 10% ethanol had significantly lower oxidative stress levels than the mucosa not pretreated with 10% ethanol. Pretreatment with 10% ethanol increased glutathione levels in the sham-operated but not in the portal hypertensive gastric mucosa. Administration of the anti-oxidant agent prior to 10% ethanol pretreatment significantly reduced oxidative stress levels, increased glutathione levels, and decreased the injury index in response to 70% ethanol in the portal hypertensive gastric mucosa. Conclusion: Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rats, probably through damage to the system of endogenous anti-oxidant production.