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.