Abstract
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.
Footnotes
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The project was partly supported by the Hong Kong Research Grant Council in Hong Kong (HKU 7281/02M).
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J.C.L. is the recipient of Physician Scientist Award from the National Health Research Institutes of Taiwan.
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DOI: 10.1124/jpet.103.055202.
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ABBREVIATIONS: PG, prostaglandin; cPLA2, cytosolic phospholipase A2; COX, cyclooxygenase; BrdU, 5-bromo-2′-deoxyuridine.
- Received June 3, 2003.
- Accepted July 29, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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