Winter, Jack Westwood
Studies of in situ nitrosative stress following nitrate ingestion in the human upper gastrointestinal tract.
MD thesis, University of Glasgow.
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Nitrate ingestion leads to high luminal concentrations of nitric oxide being generated where saliva meets gastric acid. Nitric oxide generates N-nitrosative stress on reacting with oxygen at neutral pH. We aimed to ascertain if luminal nitric oxide exerts nitrosative stress in the upper GI tract, and to assess the influence of acid reflux. We utilised a specialised silicone tube as an epithelial model, inserting it into the upper gastro-intestinal tract of humans. Healthy volunteers were studied with and without ingestion of 15N enriched nitrate and Barrett’s oesophagus patients with and without stimulation of reflux. In volunteers, nitrate ingestion resulted in significantly higher concentrations of N-nitrosomorpholine in the tube sections exposed to acid. In Barrett’s patients, generation of N-nitrosomorpholine shifted proximally, with most nitrosative stress occurring within the oesophagus during reflux episodes. This chemistry may be harmful to patients with erosive esophagitis whose epithelium will be more sensitive to chemical mutagenesis.
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