Rebamipide reduces delay in gastric ulcer healing in cyclooxygenase-2-deficient mice.
Rebamipide is an antiulcer drug capable of various actions including the induction of cyclooxygenase-2 (COX-2). In this study, we investigated the effect of rebamipide on gastric ulcer healing in COX-2-deficient mice. Wild-type (N=34) and COX-2-deficient mice (N=28) with gastric ulcers were administered 30 mg/kg of rebamipide or the vehicle. Ulcerous tissues were subjected to measurements of ulcer size, immunohistochemical staining of CD31 (an endothelial cell marker), and mRNA levels. COX-2 deficiency delayed ulcer healing and inhibited angiogenesis and bFGF mRNA expression in the granulation tissue. In wild-type mice, rebamipide accelerated ulcer healing and increased COX-2 mRNA expression. In COX-2-deficient mice, rebamipide prevented delayed ulcer healing and reversed the inhibition in angiogenesis and bFGF mRNA expression. The effect of rebamipide on the enhancement of ulcer healing, angiogenesis, and induction of bFGF expression was more prominent in wild-type mice than in COX-2-deficient mice. In conclusion, rebamipide may accelerate gastric ulcer healing through both COX-2-dependent and COX-2-independent mechanisms.
Watanabe
Toshio
T
Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. watanabet@med.osaka-cu.ac.jp
Higuchi
Kazuhide
K
Taira
Koichi
K
Sasaki
Eiji
E
Shiba
Masatsugu
M
Tominaga
Kazunari
K
Fujiwara
Yasuhiro
Y
Oshitani
Nobuhide
N
Arakawa
Tetsuo
T
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000502:physiology*; D015363:Quinolones / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000235:genetics / Q000662:veterinary
D000897:Anti-Ulcer Agents; D015363:Quinolones; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C052785:rebamipide; D000409:Alanine