Rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury in rats by inhibiting neutrophil activation.
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 (51)Cr-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.
Harada
Naoaki
N
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Okajima
Kenji
K
Liu
Wenge
W
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002199:Capillary Permeability; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D008297:Male; D018375:Neutrophil Activation; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow
D000897:Anti-Ulcer Agents; D015363:Quinolones; C052785:rebamipide; D000409:Alanine