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

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Stomach
Caspase 3
Epithelial Cells
Apoptosis
Mucous Membrane
Histamine H2 Receptors
Hyperemia
Helicobacter Infections
Virulence Factors
Nitric Oxide Synthase Type II
Gastritis
Caspases
Helicobacter pylori
Animal Models
ebrotidine
Helicobacter pylori lipopolysaccharide
Hemorrhage
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Keywords

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

Cite this

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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 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.",
keywords = "Acute gastritis, Caspase- 3, Ebrotidine, Helicobacter pylori, Lipopolysaccharide, NOS-2",
author = "Bronislaw Slomiany and J. Piotrowski and Amalia Slomiany",
year = "1999",
month = "1",
day = "1",
language = "English (US)",
volume = "50",
pages = "391--404",
journal = "Journal of Physiology and Pharmacology",
issn = "0867-5910",
publisher = "Polish Physiological Society",
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}

TY - JOUR

T1 - Effect of ebrotidine on gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide

AU - Slomiany, Bronislaw

AU - Piotrowski, J.

AU - Slomiany, Amalia

PY - 1999/1/1

Y1 - 1999/1/1

N2 - 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.

AB - 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.

KW - Acute gastritis

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KW - NOS-2

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