Effect of ebrotidine on gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide

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Abstract

Helicobacter pylori lipopolysaccharide is a primary virulence factor responsible for eliciting acute mucosal inflammatory responses associated with H. pylori infection. In this study, we applied the animal model of H. pylori lipopolysaccharide-induced acute gastritis to assess the effect of antiulcer agent, ebrotidine, on the gastric mucosal inflammatory responses by analyzing the interplay between the activity of a key apoptotic caspase, caspase-3, epithelial cell apoptosis, and the expression of inducible nitric oxide synthase (NOS-2). Methods: Rats, pretreated twice daily with ebrotidine at 100 mg/kg, or the vehicle, were subjected to intragastric application of H. pylori lipopolysaccharide at 50 μg/animal, and after 4 additional days on the antiulcer drug or vehicle regimen their mucosal tissue used for histologic assessment, assays of epithelial cells apoptosis, and the measurements of caspase-3 and NOS-2 activities. Results: In the absence of antiulcer agent, H. pylori lipopolysaccharide induced acute reaction characterized by the inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by an 11.2-fold increase in epithelial cell apoptosis, a 6.5-fold induction in mucosal expression of NOS-2, and a 5.4-fold increase in caspase-3 activity. Treatment with H2-receptor antagonist ebrotidine, also known for its gastroprotective effects, produced a 50.9% reduction in the extent of mucosal inflammatory changes elicited by H. pylori lipopolysaccharide and an 82.5% decrease in the epithelial cells apoptosis, while the activity of caspase-3 decreased by 33.7% and that of NOS-2 showed a 72.8% decline.

Original languageEnglish (US)
Pages (from-to)391-404
Number of pages14
JournalJournal of Physiology and Pharmacology
Volume50
Issue number3
StatePublished - Jan 1 1999

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Keywords

  • Acute gastritis
  • Caspase- 3
  • Ebrotidine
  • Helicobacter pylori
  • Lipopolysaccharide
  • NOS-2

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