Diflunisal protects human gastric mucosa against damage by indomethacin

Mild irritants have been shown to protect the rat gastric mucosa from damage by the subsequent administration of necrotizing agents. The purpose of this study was to determine if a low concentration of a salicyclic acid analog (8 mM diflunisal) was capable of protecting human gastric mucosa from the damage induced by topical indomethacin. Healthy young volunteers were studied in three separate experiments in which gastric transmucosal PD was used as an index of mucosal integrity. In study I (10 subjects) 20 mM aspirin and 2 mM indomethacin were shown to induce a significant (P less than 0.025) fall in PD of 15% and 10%, respectively. In study II (10 subjects) 20 mM diflunisal was found to produce no significant fall in PD nor any reduction in gastric juice PGE2. In study III (5 subjects) 8 mM diflunisal, given 15 min before 2 mM indomethacin, prevented the fall in PD caused by indomethacin alone. These studies demonstrate that in humans, 8 mM diflunisal protects the mucosa from injury induced by the subsequent administration of a known damaging agent. It is possible that the mechanism of this protection may be by stimulation of endogenous mucosal prostaglandins.