Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs.
Using the non-ulcerogenic doses of dexamethasone, we explored the action of glucocorticoids on ulcer healing and its relationship with angiogenic factors in the gastric mucosa. We applied dexamethasone (0.1 or 0.2 mg/kg/day) intragastrically in rats with acetic acid-induced gastric ulcer. The mucosal prostaglandin E(2) level and protein expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) at the ulcer margin were determined. Ulcer induction significantly increased protein expressions of bFGF, VEGF, and prostaglandin E(2) level at the ulcer margin together with angiogenesis at the ulcer margin and base. The non-ulcerogenic doses of dexamethasone inhibited angiogenesis at the ulcer margin and ulcer base and delayed ulcer healing. These were associated with a significant decrease of prostaglandin E(2) level and VEGF expression, but not the bFGF expression. Supplementation with prostaglandin E(2) attenuated the inhibitory action of dexamethasone on VEGF expression and reversed the adverse effects of dexamethasone on angiogenesis and ulcer healing, without influencing bFGF expression. We concluded that dexamethasone given at non-ulcerogenic doses could decrease angiogenesis and delay acetic acid-induced ulcer healing; these actions were at least, in part, due to depletion of prostaglandin E(2) level followed by down-regulation of VEGF at the ulcer margin of the stomach.
Luo
Jiing C
JC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University, School of Medicine, Taiwan.
Shin
Vivian Y
VY
Liu
Edgar S L
ES
Ye
Yi N
YN
Wu
William K K
WK
So
Wallace H L
WH
Chang
Full Y
FY
Cho
Chi H
CH
D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000378:metabolism / Q000503:physiopathology*
D020533:Angiogenesis Inhibitors; D003907:Dexamethasone