Role of Acid and Salivary Epidermal Growth Factor in Gastric Mucosal Adaptation to Naproxen in Man

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the gastrointestinal tract, but with continued administration this usually resolves by a process of adaptation. There is evidence that the acute injury can be reduced by acid suppression, and animal models have shown that salivary epidermal growth factor (EGF) is an important factor in gastric mucosal adaptation. We therefore wanted to assess the effect of acid suppression and salivary EGF output during naproxen-induced acute gastric injury and subsequent adaptation. Methods: Healthy subjects were given a 14-day course of naproxen with different regimens of ranitidine and placebo. Before and on three occasions during treatment subjects provided a salivary sample for EGF and underwent gastroscopy to assess gastric damage. Results: Similar gastric damage occurred after 24 h in all groups and resolved in most subjects. Base-line salivary EGF output was similar in all groups but increased in the placebo/ranitidine group on day 3 and in the ranitidine group on day 9. Conclusions: Acid suppression with ranitidine did not prevent acute gastric injury. Adaptation may be associated with an increase in salivary EGF output.