Stress, diet and alcohol-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate.

Oxygen free radicals are implicated in the pathogenesis of stress and food/alcohol-induced gastrointestinal injury. We have investigated the effects of restraint stress, spicy food diet, high-fat diet and 40% ethanol on the enhanced production of reactive oxygen species, including superoxide anion and hydroxyl radicals, and on DNA fragmentation, lipid peroxidation and membrane microviscosity (indices of oxidative tissue damage) in gastric and intestinal mucosa of Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS; 15 mg kg(-1) was determined against the gastrointestinal mucosal injury induced by these stressors. Animals on the high-fat diet consumed 31% more food as compared to other animals. Animals on the spicy food diet consumed ca. 23% more water as compared to control animals, and the high-fat diet animals consumed 17% less water. Restraint stress provided greater injury to both gastric and intestinal mucosa as compared to other stressors. Restraint stress, spicy food diet, high-fat diet and ethanol increased superoxide anion production by 10.0-, 4.3-, 5.7- and 4.8-fold, respectively, in the gastric mucosa, and by 10.4-, 5.3-, 7.0- and 5.5-fold in the intestinal mucosa. Exposure to restraint stress, spicy food diet, high-fat diet and 40% ethanol also increased hydroxyl radical production by ca. 14.3-, 4.5-, 3.5- and 4.8-fold, respectively, in the gastric mucosa, and by 17.0-, 4.8-, 3.5- and 4.7-fold in the intestinal mucosa. Bismuth subsalicylate administration to the animals provided significant protection against superoxide anion and hydroxyl radical production. Restraint stress, spicy food diet, high-fat diet and ethanol increased lipid peroxidation by 3.6-, 2.4-, 2.6- and 2.0-fold, respectively, in the gastric mucosa, and by 4.1-, 3.5-, 3.6- and 2.7-fold in intestinal mucosa. Administration of BSS decreased restraint stress, spicy food diet, high-fat diet and ethanol-induced gastric mucosal lipid peroxidation by ca. 26%, 36%, 45% and 18%, and intestinal mucosa lipid peroxidation by 20%, 21%, 46% and 42%, respectively. Approximately 4.0-, 2.0-, 2.4- and 2.0-fold increases in DNA fragmentation were observed in the gastric mucosa of rats exposed to restraint stress, spicy food diet, high-fat diet and 40% ethanol, respectively, and similar increases in the intestinal mucosa. These same four stressors increased membrane microviscosity by 11.6-, 6.1-, 7.3- and 5.4-fold, respectively, in the gastric mucosa, and by 16.2-, 7.9-, 9.5- and 7.8-fold in the intestinal mucosa. Bismuth subsalicylate exerted significant protection against DNA damage and changes in membrane microviscosity induced by the four stressors. Excellent correlations existed between the production of reactive oxygen species and the tissue damaging effects in both gastric and intestinal mucosa. In summary, the results demonstrate that physical and chemical stressors can induce gastrointestinal oxidative stress and mucosal injury through enhanced production of reactive oxygen species, and that BSS can significantly attenuate gastrointestinal injury by scavenging these reactive oxygen species.