ESOPHAGITIS IN SPRAGUE-DAWLEY RATS IS MEDIATED BY FREE-RADICALS

Free radical-mediated esophagitis was studied during duodenogastroesop hageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflu x caused more gross mucosal injury than acid reflux. Gross mucosal inj ury occurred in the mid-esophagus. Total glutathione (GSH) in the esop hageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mix ed than in the acid reflux group. The free radical scavenger superoxid e dismutase (SOD) prevented esophagitis and was associated with decrea sed GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevente d esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidat ive stress in the esophageal mucosa. The lower GSH levels in the mid-e sophagus may predispose to damage in this area. Duodenogastroesophagea l reflux causes more damage than pure acid reflux. Oxidative stress le ads to GSH depletion of the esophageal mucosa in the first few hours f ollowing damage but then stimulates GSH production. GSH depletion by B SO does not worsen esophagitis since it increases the esophageal SOD c oncentration.