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Rebamipide Reduces Delay in Gastric Ulcer Healing in Cyclooxygenase-2-Deficient Mice

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Abstract

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.

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Authors and Affiliations

  1. Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan

    Toshio Watanabe MD, PhD, Kazuhide Higuchi MD, PhD, Koichi Taira MD, Eiji Sasaki MD, PhD, Masatsugu Shiba MD, PhD, Kazunari Tominaga MD, PhD, Yasuhiro Fujiwara MD, PhD, Nobuhide Oshitani MD, PhD & Tetsuo Arakawa MD, PhD

Authors
  1. Toshio Watanabe MD, PhD
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  2. Kazuhide Higuchi MD, PhD
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  3. Koichi Taira MD
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  4. Eiji Sasaki MD, PhD
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  5. Masatsugu Shiba MD, PhD
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  6. Kazunari Tominaga MD, PhD
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  7. Yasuhiro Fujiwara MD, PhD
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  8. Nobuhide Oshitani MD, PhD
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  9. Tetsuo Arakawa MD, PhD
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Correspondence to Toshio Watanabe MD, PhD.

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Watanabe, T., Higuchi, K., Taira, K. et al. Rebamipide Reduces Delay in Gastric Ulcer Healing in Cyclooxygenase-2-Deficient Mice. Dig Dis Sci 50 (Suppl 1), S63–S69 (2005). https://doi.org/10.1007/s10620-005-2808-1

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  • DOI: https://doi.org/10.1007/s10620-005-2808-1

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