Non-Ulcerogenic Dose of Dexamethasone Delays Gastric Ulcer Healing in Rats
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 mechan...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 307; no. 2; pp. 692 - 698 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.11.2003
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Subjects | |
Online Access | Get full text |
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Summary: | 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 A 2 (cPLA 2 ) over the ulcer margin were evaluated, and the mucosal prostaglandin E 2 (PGE 2 ) 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 PGE 2 level but not COX-1 at the ulcer margin. The drug only marginally reduced the cPLA 2 expression without affecting the apoptosis at the ulcer margin. PGE 2 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 PGE 2 formation in the gastric mucosa. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.103.055202 |