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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Non-Ulcerogenic Dose of Dexamethasone Delays Gastric Ulcer Healing in Rats

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taipei, Taiwan (J.C.L., F.Y.C.); and Department of Pharmacology, Faculty of Medicine, the University of Hong Kong, Hong Kong, China (V.Y.S., E.S.L.L., W.H.L.S., Y.N.Y., C.H.C.)

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.

Address correspondence to: Prof. C. H. Cho, Department of Pharmacology, Faculty of Medicine, 2nd Floor, Laboratory Block, The University of Hong Kong, 21 Sassoon Rd., Hong Kong, China. E-mail: chcho{at}hkusua.hku.hk

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