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Rebamipide Decreases the Susceptibility of Gastric Mucosa to Acid-Induced Injury in Rats by Inhibiting Neutrophil Activation

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Abstract

We previously demonstrated that activated neutrophils increased the susceptibility of gastric mucosa to acid-induced injury in rats. As rebamipide, an anti-ulcer agent, inhibits neutrophil activation, we examined whether the rebamipide reduces stress-induced gastric mucosal injury by decreasing susceptibility to acid-induced gastric mucosal injury in rats. Increase in both gastric mucosal permeability and gastric microvascular permeability evaluated by 51Cr-EDTA clearance and Evans blue leakage, respectively, at 6 hr after Water-Immersion Restraint Stress (WIR) were significantly lower in animals with leukocytopenia than those in controls. Pretreatment with neutrophil elastase (NE) inhibitors, an anti-P-selectin monoclonal antibody (MAb), and rebamipide significantly inhibited these increases at 6 hr after WIR. These treatments also inhibited decrease in gastric mucosal blood flow observed at 6 hr after WIR. Acid-induced exacerbation of gastric mucosal injury in rats at 6 hr after WIR was inhibited by NE inhibitors, anti-P-selectin MAb, and rebamipide. Rebamipide significantly inhibited WIR-induced increase in gastric MPO activity at 8 hr after WIR. Observations in the present study raised a possibility that rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury by inhibiting neutrophil activation.

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Authors and Affiliations

  1. Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Naoaki Harada MD, Kenji Okajima MD & Wenge Liu PhD

Authors
  1. Naoaki Harada MD
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  2. Kenji Okajima MD
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  3. Wenge Liu PhD
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Correspondence to Kenji Okajima MD.

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Harada, N., Okajima, K. & Liu, W. Rebamipide Decreases the Susceptibility of Gastric Mucosa to Acid-Induced Injury in Rats by Inhibiting Neutrophil Activation. Dig Dis Sci 50 (Suppl 1), S56–S62 (2005). https://doi.org/10.1007/s10620-005-2807-2

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  • DOI: https://doi.org/10.1007/s10620-005-2807-2

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