Superoxide anions produced by inflammatory cells play an important part in the pathogenesis of acid and pepsin induced oesophagitis in rabbits.
BACKGROUND
Reactive oxygen metabolites have been associated with gastrointestinal injury.


OBJECTIVE
To investigate whether mucosal reactive oxygen metabolites are involved in acid and pepsin induced oesophagitis, and if so, which specific metabolites.


METHODS
The effects of free radical scavengers and the anti-inflammatory drug ketotifen on rabbit oesophagitis induced by acidified pepsin were studied. Isolated oesophageal cells were obtained before and after oesophageal injury and the generation of superoxide anion and hydrogen peroxide was analysed by flow cytometry. The presence of inflammatory cells was determined by indirect immunofluorescence with a mouse antirabbit CD11b antibody.


RESULTS
Of the free radical scavengers tested, superoxide dismutase, which reacts with the superoxide anion, significantly reduced oesophagitis, whereas catalase, which reacts with hydrogen peroxide, had only a mild effect and dimethylsulphoxide had no effect. Ketotifen significantly reduced the inflammation and also prevented the induction of oesophagitis. Isolated cells obtained from the oesophageal mucosa after acidified pepsin exposure generated increased amounts of superoxide anions, which were mainly produced by CD11b positive cells.


CONCLUSIONS
Reactive oxygen metabolites, especially superoxide anion, produced by inflammatory cells play a significant part in the genesis of oesophagitis induced by acid and pepsin in rabbits and might be a target for future medical therapy.
Naya
M J
MJ
Gastroenterology Services, University of Zaragoza, Spain.
Pereboom
D
D
Ortego
J
J
Alda
J O
JO
Lanas
A
A
D000818:Animals; D000838:Anions; D002374:Catalase / Q000627:therapeutic use; D002478:Cells, Cultured; D004941:Esophagitis / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004947:Esophagus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D007249:Inflammation; D007665:Ketotifen / Q000627:therapeutic use*; D016177:Macrophage-1 Antigen / Q000032:analysis; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010434:Pepsin A / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism*
D000838:Anions; D016166:Free Radical Scavengers; D006634:Histamine H1 Antagonists; D016177:Macrophage-1 Antigen; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D010434:Pepsin A; D007665:Ketotifen