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Exogenous luminal nitric oxide exacerbates esophagus tissue damage in a reflux esophagitis model of rats.
- Source :
-
Scandinavian journal of gastroenterology [Scand J Gastroenterol] 2009; Vol. 44 (5), pp. 527-37. - Publication Year :
- 2009
-
Abstract
- Objective: Cytotoxic concentrations of nitric oxide are generated luminally at the gastroesophageal junction through the entero-salivary recirculation of dietary nitrate in humans. The site of luminal nitric oxide generation shifts to the lower esophagus when gastric acid is refluxed into the esophagus. The aim of this study was to investigate the influence of persistent administration of exogenous nitric oxide on esophageal damage.<br />Material and Methods: 0.1% sodium nitrite and/or 1% ascorbic acid was administered in an established rat acid-refluxed esophagitis model. Co-administration of both reactants in this model is thought to induce high concentrations of nitric oxide luminally in the esophagus by an acid-catalyzed chemical reaction when refluxed gastric acid is present. The tissue damage was evaluated by a macroscopic lesion index and myeloperoxidase activity. Nitrotyrosin was assessed immunohistochemically as a footprint of peroxynitrite formation.<br />Results: Co-administration of sodium nitrite and ascorbic acid induced a 4- to 5-fold increase in the esophageal damage compared with baseline reflux esophagitis, while the damage was unchanged when either of the reagents alone was given. Nitrotyrosine was strongly stained in the tissue from the co-administration. Treatment of superoxide scavengers efficiently prevented the exacerbation of esophageal damage by exogenous nitric oxide exposure, suggesting an essential role of superoxide in esophageal damage.<br />Conclusions: Exogenous luminal nitric oxide greatly exacerbated the tissue damage of reflux esophagitis. Diffusion of the luminal nitric oxide into the adjacent superoxide-enriched inflamed tissue of the esophagus could lead to the production of the highly toxic agent peroxynitrite, thus causing exacerbation of the esophageal damage.
- Subjects :
- Analysis of Variance
Animals
Ascorbic Acid adverse effects
Biopsy, Needle
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Drug Therapy, Combination
Esophagitis, Peptic physiopathology
Esophagogastric Junction pathology
Immunohistochemistry
Male
Nitric Oxide pharmacology
Peroxidase metabolism
Probability
Random Allocation
Rats
Rats, Wistar
Sensitivity and Specificity
Ascorbic Acid pharmacology
Esophagitis, Peptic drug therapy
Esophagitis, Peptic pathology
Esophagogastric Junction drug effects
Nitric Oxide adverse effects
Omeprazole pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1502-7708
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Scandinavian journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 19172433
- Full Text :
- https://doi.org/10.1080/00365520802699260