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 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.
Luo
Jiing C
JC
Department of Pharmacology, Faculty of Medicine, 2nd Floor, Laboratory Block, The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
Shin
Vivian Y
VY
Liu
Edgar S L
ES
So
Wallace H L
WH
Ye
Yi N
YN
Chang
Full Y
FY
Cho
Chi H
CH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D051545:Cyclooxygenase 1; D003907:Dexamethasone / Q000009:adverse effects*; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000201:enzymology / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone