Reactive oxygen metabolites and upper gastrointestinal diseases.
Reactive oxygen metabolites play an important role in the pathogenesis of gastroduodenal mucosal inflammation (mucosal ischemic injury and other models of mucosal damage induced by nonsteroidal anti-inflammatory drugs, ethanol, or H. pylori), peptic ulcer disease, and gastric cancer. H. pylori achieves its pathogenetic role by triggering an intense leukocyte infiltration of the gastric mucosa, and neutrophil activation provides a major source of reactive oxygen metabolites which can cause tissue damage mainly in the absence of antioxidants. H. pylori virulence factors promote release of a variety of chemoattractants/inflammatory mediators. Circulating leukocytes are recruited to sites of inflammation by a well-regulated and coordinated process that largely occurs in postcapillary venules. Adhesion molecules are expressed on the surface of endothelial cells and leukocytes serve to ensure an orderly sequence of cell-to-cell interactions that sustain leukocyte adherence to vascular endothelium and the subsequent transendothelial migration into inflamed tissue. Transcriptional factors are involved in the expression of endothelial adhesion molecules, and regulation of activity of these factors (i.e., NF-kappa B) is a very attractive target for therapeutic interventions. Longstanding H. pylori-associated gastritis predisposes to gastric cancer development and reactive oxygen metabolites play a part in H. pylori-related gastric carcinogenesis. Various regimens of reactive oxygen metabolite scavengers appear to be new treatment strategies for upper gastrointestinal diseases.
Kountouras
J
J
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital Thessaloniki, Greece. jannis@med.auth.gr
Chatzopoulos
D
D
Zavos
C
C
D000818:Animals; D005753:Gastric Mucosa / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013272:Stomach Diseases / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology; D014774:Virulence
D017382:Reactive Oxygen Species