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

Abstract

UNLABELLED:

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: B L Slomiany, J Piotrowski, A Slomiany
• Journal: Journal of physiology and pharmacology : an official journal of the Polish Physiological Society (J Physiol Pharmacol) Vol. 50 Issue 3 Pg. 391-404 (Sep 1999) ISSN: 0867-5910 [Print] Poland
• PMID: 10574469 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Benzenesulfonates
• Lipopolysaccharides
• Thiazoles
• ebrotidine

Topics

• Acute Disease
• Animals
• Anti-Ulcer Agents (pharmacology)
• Benzenesulfonates (pharmacology)
• Disease Models, Animal
• Gastric Mucosa (drug effects, enzymology, pathology)
• Gastritis (drug therapy, microbiology, pathology)
• Helicobacter Infections (drug therapy, microbiology, pathology)
• Helicobacter pylori
• Lipopolysaccharides (toxicity)
• Rats
• Rats, Sprague-Dawley
• Thiazoles (pharmacology)