Role of intragastric pH in cytoprotection by antacids in rats

Antacids containing Al(OH)3 have been shown to stimulate the protective and reparative processes in the gastric mucosa exposed to various ulcerogens but the mechanisms of these effects are unknown. This study was designed to determine the role of intragastric pH and mucosal formation of prostaglandins (PG) in antacid-induced protection of gastric mucosa against ethanol or aspirin damage. Maalox 70 and its active component, Al(OH)3, were used alone at the original pH (7.5 and 6.0, respectively) and lower pH or were combined with ranitidine or histamine before intragastric administration of 100% ethanol or acidified aspirin to induce acute mucosal lesions. Maalox and Al(OH)3 were relatively more effective to protect against the damage due to ethanol, and to some extent also due to aspirin, when given at a pH (pH 2) lower than at their original pH. Pretreatment with ranitidine, which itself did not change ethanol-induced damage, greatly reduced the protection afforded by Maalox or Al(OH)3, whereas pretreatment with histamine enhanced this protection. Maalox and Al(OH)3 at their original or low pH did not alter significantly the capability of gastric mucosa to generate PG but resulted in a significant increase in luminal release of PG. Pretreatment with indomethacin to reduce mucosal generation of PG failed to affect the protective effects of Maalox or Al(OH)3 at their original or lower pH. We conclude that Maalox 70 and Al(OH)3 protect the gastric mucosa against ethanol damage but that this protection requires the presence of acid and may not depend entirely upon the mucosal production of PG.