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OESOPHAGUS |
University of Glasgow, Glasgow, UK
Correspondence to:
Correspondence to:
Professor K E L McColl
Section of Medicine, Western Infirmary, 44 Church St, Glasgow G11 6NT, UK; K.E.L.McColl{at}clinmed.gla.ac.uk
Background and aims: When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide. In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia. We have studied the location of this luminal chemistry in Barretts patients during acid reflux.
Methods: Ten Barretts patients were studied before and after administration of 2 mmol nitrate. Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barretts segment, hiatal sac, proximal stomach, and distal stomach. In a subgroup, real time nitric oxide concentrations were also measured.
Results: During acid reflux, Barretts segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate. Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites. On entering the acidic Barretts segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site. Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 µM within the Barretts segment.
Conclusion: The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barretts oesophagus.
Keywords: Barretts oesophagus; nitrate; nitrite; nitrosation; nitric oxide; gastro-oesophageal reflux disease; oesophageal cancer
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Gut 2005 54: 1509.
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