Acceleration of recovery of gastric epithelial integrity by 16,16‐dimethyl prostaglandin E₂

Abstract

The effects of pretreatment with 16,16‐dimethyl prostaglandin E2 (DmPGE2) on the recovery of gastric mucosal ‘barrier’ parameters after ethanol‐induced damage were studied using an ex vivo chamber preparation in the rat. DmPGE2 (4–40 μg kg−1) significantly reduced the extent of haemorrhagic damage to the gastric mucosa induced by the topical application of 50% ethanol followed by 0.05 M hydrochloric acid. The lowest dose of DmPGE2 tested (4 μg kg−1) had no effect on the ethanol‐induced changes in transmucosal potential difference (PD) or K+ efflux. However, DmPGE2 at doses at 20 or 40 μg kg−1 significantly reduced the changes in these indices of epithelial integrity. The recovery of PD and K+ efflux to control levels after ethanol‐injury was accelerated by DmPGE2. With the two higher doses of DmPGE2 (20 and 40 μg kg−1) there was a significantly (P < 0.001) lower level of epithelial discontinuity, measured histologically, in samples taken at the end of the experiment. These results suggest that at the higher doses, DmPGE2 confers some protection to the gastric epithelium as well as accelerating the recovery of epithelial integrity after damage induced by ethanol.

Repair of Mucosal Damage Induced by Ethanol in the Rat Stomach

“…It has been shown that exogenously ad ministered PGs significantly accelerate the recovery of the epithelial integrity in the rat stomach after exposure to 50 or 100% etha nol [18,19], The present study confirmed the above findings and further showed that endogenous PGs may be involved in the cel lular events associated with the mucosal res toration. Indomethacin, a cyclooxygenase inhibitor, delayed the recovery of PD after exposure to 50% ethanol, and this effect was completely reverted by concurrent adminis tration of 16,16-dmPGE2.…”

Aspirin causes rapid up‐regulation of cyclo‐oxygenase‐2 expression in the stomach of rats

“…1, 2 Indeed, prostaglandins have been shown to be important mediators of epithelial restitution in the stomach, 28,29 and their importance in repair of ulcers is underscored by the marked ability of NSAIDs to interfere with this process. 30,31 While it is now clear that there are at least two isoforms of cyclooxygenase (the principle enzyme responsible for prostaglandin synthesis), the relative contribution of each isoform to mucosal prostaglandin synthesis in various circumstances is not clear.…”