PT - JOURNAL ARTICLE AU - Jiing C. Luo AU - Vivian Y. Shin AU - Edgar S. L. Liu AU - Wallace H. L. So AU - Yi N. Ye AU - Full Y. Chang AU - Chi H. Cho TI - Non-Ulcerogenic Dose of Dexamethasone Delays Gastric Ulcer Healing in Rats AID - 10.1124/jpet.103.055202 DP - 2003 Nov 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 692--698 VI - 307 IP - 2 4099 - http://jpet.aspetjournals.org/content/307/2/692.short 4100 - http://jpet.aspetjournals.org/content/307/2/692.full SO - J Pharmacol Exp Ther2003 Nov 01; 307 AB - Although the ulcerogenic action of corticosteroids in the stomach is controversial, its action on ulcer healing has not been defined. In this study, we used non-ulcerogenic doses of dexamethasone (0.1 or 0.2 mg/kg/day) to explore the adverse effect on ulcer healing as well as its pathological mechanisms in rat stomach. In this regard, we measured ulcer size, mucus thickness, epithelial cell proliferation and apoptosis, and angiogenesis at the ulcer site at different time points after ulcer induction. Protein expressions of cyclooxygenase-1 and -2 (COX-1 and COX-2) and cytosolic phospholipase A2 (cPLA2) over the ulcer margin were evaluated, and the mucosal prostaglandin E2 (PGE2) level was also determined. Dexamethasone treatment in the current doses did not produce mucosal damage in intact animals. However, the drug dose-dependently delayed gastric ulcer healing. It also decreased mucus content and epithelial cell proliferation at the ulcer margin as well as angiogenesis at the ulcer margin and base. These were associated with a significant decrease of COX-2 expression and PGE2 level but not COX-1 at the ulcer margin. The drug only marginally reduced the cPLA2 expression without affecting the apoptosis at the ulcer margin. PGE2 treatment reversed the adverse effects of dexamethasone on ulcer healing. It is concluded that nonulcerogenic doses of dexamethasone can delay ulcer repair via depression of COX-2 expression and PGE2 formation in the gastric mucosa. The American Society for Pharmacology and Experimental Therapeutics