Acute and chronic stress-induced oxidative gastrointestinal mucosal injuryin rats and protection by bismuth subsalicylate

Reactive oxygen species (ROS) are implicated in the pathogenesis of stress- induced gastrointestinal mucosal injury. In the present study, we have inve stigated the effects of acute and chronic stress on the enhanced production of ROS including superoxide anion [SA; as determined by cytochrome c reduc tion (CCR)] and hydroxyl radicals (OH), and correlated the enhanced product ion of these free radicals with increased lipid peroxidation, membrane micr oviscosity and DNA fragmentation, indices of oxidative tissue damage, in th e gastric and intestinal mucosa of female Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS) against the gastroin testinal mucosal injury induced by acute and chronic stress was determined. Acute stress was induced for a period of 90 min, while chronic stress was induced for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 15 mg BSS/kg 30 min prior to t he exposure to acute stress. Similarly, half of the animals exposed to wate r-immersion restraint chronic stress were pretreated orally with 7.5 mg BSS /kg/day for 15 consecutive days 30 min prior to the exposure to chronic str ess. Acute stress produced greater injury to both gastric and intestinal mu cosa as compared to chronic stress. Acute stress increased CCR and OH produ ction by 10.0- and 14.3-fold, respectively, in the gastric mucosa, and 10.4 - and 17.0-fold, respectively, in the intestinal mucosa. Pretreatment with BSS prevented the acute stress-induced increase in CCR and OH production. A cute stress increased lipid peroxidation, DNA fragmentation and membrane mi croviscosity by 3.6-, 4.0- and 11.6-fold, respectively, in gastric mucosa, and 4.1-, 5.0- and 16.2-fold, respectively, in intestinal mucosa. BSS decre ased acute stress-induced lipid peroxidation, DNA fragmentation and membran e microviscosity by approximately 26, 35 and 30%, respectively, in gastric mucosa, and by 20, 36 and 30%, respectively, in the intestinal mucosa. Chro nic stress increased CCR and OH production by 4.8- and 6.3-fold, respective ly, in gastric mucosa, and 4.6- and 6.9-fold, respectively, in intestinal m ucosa. Chronic stress increased lipid peroxidation and DNA fragmentation by 2.9- and 3.3-fold, respectively, in gastric mucosa, and 3.3- and 4.2-fold, respectively, in intestinal mucosa. BSS decreased chronic stress-induced l ipid peroxidation, DNA fragmentation and membrane microviscosity by approxi mately 41, 44 and 45%, respectively, in gastric mucosa, and by 39, 52 and 5 1%, respectively, in the intestinal mucosa. Daily administration of BSS pro vided greater protection against chronic stress-induced oxidative gastroint estinal injury as compared to the acute stress. These results demonstrate t hat both acute and chronic stress can induce gastrointestinal mucosal injur y through enhanced production of ROS, and that BSS can significantly protec t against gastrointestinal mucosal injury.