title: Effect of ebrotidine on gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide.
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 microg/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.
  
  
  CONCLUSIONS
  The findings implicate caspase-3 involvement in gastric mucosal inflammatory responses to H. pylori lipopolysaccharide, and point towards participation of NOS-2 in the amplification of the cell death-signaling cascade. Our study also demonstrate that ebrotidine exerts modulatory effect on the H. pylori-induced mucosal inflammatory responses by interfering with the events propagated by NOS-2 and caspase-3.
authors.affiliation: Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: J
authors.initials: J
authors.lastname: Piotrowski
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000208:Acute Disease; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005756:Gastritis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori; D008070:Lipopolysaccharides / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000897:Anti-Ulcer Agents; D001557:Benzenesulfonates; D008070:Lipopolysaccharides; D013844:Thiazoles; C075156:ebrotidine