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Involvement of luminal nitric oxide in the pathogenesis of the gastroesophageal reflux disease spectrum.
- Source :
-
Journal of gastroenterology and hepatology [J Gastroenterol Hepatol] 2014 May; Vol. 29 (5), pp. 898-905. - Publication Year :
- 2014
-
Abstract
- Over the last 3 decades, the incidence of esophageal adenocarcinoma has dramatically increased in Western countries; a similar increase may be observed in Asian countries in the near future. Esophageal adenocarcinoma arises from a sequential gastroesophageal reflux disease (GERD) spectrum from reflux erosive esophagitis, to Barrett's esophagus, and finally to esophageal adenocarcinoma. At present, gastric acid and bile are assumed to be primarily involved in the etiology of the GERD spectrum. We reported in 2002 that, at the gastroesophageal junction in humans, abundant amounts of nitric oxide (NO) are generated luminally through the entero-salivary re-circulation of dietary nitrate. Since then, we have carried out a series of experiments to demonstrate that NO diffuses into the adjacent epithelium at cytotoxic levels. This diffusion results in disruption of the epithelial barrier function, exacerbation of inflammation, acceleration of columnar transformation in the esophagus (Barrett's esophagus) via the induction of caudal-type homeobox 2, and the shifting of carcinogenic N-nitroso compound formation from the luminal to epithelial compartment. These results suggest that, in addition to conventionally recognized causative factors, luminal NO could also be involved in the pathogenesis of the GERD spectrum. In addition, we recently showed that there is a prominent gender-related difference in NO-related cytotoxicity in the esophagus and that estrogen attenuated the esophageal tissue damage via the estrogen receptor in female rats. The role of estrogen in attenuating the esophageal tissue damage in NO-related esophageal damage could explain the well-recognized male predominance in the GERD spectrum in humans.<br /> (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)
- Subjects :
- Adenocarcinoma etiology
Animals
Barrett Esophagus etiology
Bile
Epithelium metabolism
Esophageal Neoplasms etiology
Esophagogastric Junction metabolism
Estrogens physiology
Female
Gastric Acid
Humans
Male
Rats
Sex Characteristics
Gastroesophageal Reflux etiology
Nitric Oxide metabolism
Nitric Oxide toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1440-1746
- Volume :
- 29
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of gastroenterology and hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 24863184
- Full Text :
- https://doi.org/10.1111/jgh.12548