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Rebamipide Reduces Indomethacin-Induced Gastric Injury in Mice via Down-Regulation of ICAM-1 Expression

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Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Tetsuro Hiratsuka MD, Seiji Futagami MD, PhD, Tomotaka Shindo MD, Tatsuhiko Hamamoto MD, Nobue Ueki MD, Kenji Suzuki MD, Yoko Shinji MD, Masanori Kusunoki MD, Kei Shinoki MD, Ken Wada MD, PhD, Kazumasa Miyake MD, PhD, Katya Gudis MS, Taku Tsukui MD, PhD & Choitsu Sakamoto MD, PhD

Authors
  1. Tetsuro Hiratsuka MD
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  2. Seiji Futagami MD, PhD
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  3. Tomotaka Shindo MD
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  4. Tatsuhiko Hamamoto MD
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  5. Nobue Ueki MD
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  6. Kenji Suzuki MD
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  7. Yoko Shinji MD
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  8. Masanori Kusunoki MD
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  9. Kei Shinoki MD
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  10. Ken Wada MD, PhD
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  11. Kazumasa Miyake MD, PhD
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  12. Katya Gudis MS
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  13. Taku Tsukui MD, PhD
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  14. Choitsu Sakamoto MD, PhD
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Corresponding author

Correspondence to Choitsu Sakamoto MD, PhD.

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Hiratsuka, T., Futagami, S., Shindo, T. et al. Rebamipide Reduces Indomethacin-Induced Gastric Injury in Mice via Down-Regulation of ICAM-1 Expression. Dig Dis Sci 50 (Suppl 1), S84–S89 (2005). https://doi.org/10.1007/s10620-005-2811-6

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  • DOI: https://doi.org/10.1007/s10620-005-2811-6

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