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% e thanol on the enhanced production of reactive oxygen species, includin g superoxide anion and hydroxyl radicals, and on DNA fragmentation, li pid peroxidation and membrane microviscosity (indices of oxidative tis sue damage) in gastric and intestinal mucosa of Sprague-Dawley rats. F urthermore, the protective ability of bismuth subsalicylate (BSS; 15 m g 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 h igh-fat diet animals consumed 17% less water. Restraint stress provide d 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 hydrox yl radical production by ca. 14.3-, 4.5-, 3.5- and 4.8-fold, respectiv ely, in the gastric mucosa, and by 17.0-, 4.8-, 3.5- and 4.7-fold in t he intestinal mucosa. Bismuth subsalicylate administration to the anim als provided significant protection against superoxide anion and hydro xyl radical production. Restraint stress, spicy food diet, high-fat di et 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- a nd 2.7-fold in intestinal mucosa. Administration of BSS decreased rest raint stress, spicy food diet, high-fat diet and ethanol-induced gastr ic mucosal lipid peroxidation by ca. 26%, 36%, 45% and 18%, and intest inal mucosa lipid peroxidation by 20%, 21%, 46% and 42%, respectively. Approximately 4.0-, 2.0-, 2.4- and 2.0-fold increases in DNA fragment ation 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 stres sors increased membrane microviscosity by 11.6-, 6.1-, 7.3- and 5.4-fo ld, respectively, in the gastric mucosa, and by 16.2-, 7.9-, 9.5- and 7.8-fold in the intestinal mucosa. Bismuth subsalicylate erected signi ficant protection against DNA damage and changes in membrane microvisc osity induced by the four stressors. Excellent correlations existed be tween the production of reactive oxygen species and the tissue damagin g effects in both gastric and intestinal mucosa. In summary, the resul ts demonstrate that physical and chemical stressors can induce gastroi ntestinal oxidative stress and mucosal injury through enhanced product ion of reactive oxygen species, and that BSS can significantly attenua te gastrointestinal injury by scavenging these reactive oxygen species . (C) 1998 John Wiley & Sons, Ltd.