Gastric adaptation to aspirin and stress enhances gastric mucosal resistance against the damage by strong irritants

Abstract

Background: Gastric mucosal adaptation to injury induced by repeated application of aspirin (ASA) or stress is a well-documented phenomenon, but it is known whether such adaptation affects the mucosal tolerance to other strong irritants.

Methods: In this study gastric adaptation was induced by repeated daily administration of acidified ASA for 4 consecutive days (Series A) or by 3.5H of water immersion and restraint stress (WRS) applied every other day for up to 8 days (series B). When the adaptation to ASA or WRS was fully developed, rats of series A and B were challenged with strong irritants such as 100% ethanol, 200 mM acidified taurocholate (TC), or 25% NaCl for 1 h or with WRS for 3.5 h.

Results: ASA or WRS applied once produced numerous gastric lesions and deep histologic necrosis accompanied by a decrease in gastric blood flow. With repeated application of ASA or stress the mucosal adaptation to ASA and WRS developed; the area of gastric lesions was reduced by 86% and 56%, respectively, and this was accompanied by a marked decrease of superficial and deep necrosis, and increase in gastric blood flow (GBF) and the enhancement of mucosal regeneration. An increase in mucosal and luminal contents of epidermal growth factor (EGF) and in mucosal expression of EGF receptors was also observed in the mucosa adapted to ASA or stress. In rats adapted to ASA or stress and then challenged with 100% ethanol, 200 mm TC, 25% NaCl, stress or ASA, the areas of macroscopic gastric lesions and deep histologic necrosis were remarkable reduced as compared with those in non-adapted vehicle-treated rats. This was also accompanied by a significant decrease in (GBF), a marked increase of mucosal and luminal contents of EGF and expression of its receptors, and enhanced mucosal cell proliferation.

Conclusions: Gastric adaptation to ASA or stress enhances mucosal resistance to the injury induced by strong irritants, and this appears to be mediated by mucosal regeneration, probably resulting from increased luminal and mucosal contents of EGF and excessive expression of its receptors.