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Influence of dietary antioxidants on luminal nitrite chemistry under conditions simulating the gastro-oesophageal junction

Elmesmari, Aziza Atiya (2009) Influence of dietary antioxidants on luminal nitrite chemistry under conditions simulating the gastro-oesophageal junction. MSc(R) thesis, University of Glasgow.

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Abstract

Abstract The second half of the twenties century saw a sharp worldwide decline in the both incidence and mortality of gastric cancer. Despite this the condition remains the world’s second leading cause of cancer mortality, second only to lung cancer. Although most gastric cancers arise in the antrum and body (non-cardia) of the stomach, the incidence of proximal tumours of the cardia and distal oesophagus have increased dramatically over the last fifty years throughout the world. This major change in the pattern of the disease suggests that gastric cancer (cardia versus non-cardia) is not one but two separate disorders with regard to cause and pathogenesis. Over the last fifty years there has been concern about luminal nitrite, derived from dietary nitrate, as a risk factor for upper gastro-intestinal malignancies. This has arisen from evidence that the salivary nitrite is rapidly converted to nitrosating species and (in the presence of ascorbic acid) nitric oxide (NO), which are both potentially mutagenics. Thus this study aimed to investigate the influence of ascorbic acid (AA), sodium thiocyanate (NaSCN), oxygen (O2) and pH (1.5, 2.5 and 3.0) on the nitrite chemistry in simulated gastric juice. Another aim of the present study was to investigate the influence of a range of water-soluble dietary phenolics antioxidants on the nitrite chemistry to compare their effect with that of ascorbic acid. The capacity of dietary phenolics and ascorbic acid to reduce the acidified nitrite to nitric oxide was also investigated under both aerobic and anaerobic conditions. These studies were performed in a newly designed closed bench-top model reproducing the chemical environment occurring at the human gastro-oesophageal junction. Each of the experiments was performed with and without NaSCN at different pH values (1.5, 2.5 and 3.0) under both aerobic and anaerobic conditions. The studies were focused on the measurement of NO formation and O2 consumption by electrochemical detection, according to the antioxidant present in the system (ascorbic acid, ferulic acid, caffeic acid, gallic acid or chlorogenic acid, in a range of concentrations). Nitric oxide production increased with increasing ascorbic acid concentration, and was greatest at the lowest pH of 1.5. The absence of oxygen in the system markedly increased nitric oxide levels in the presence of ascorbic acid, while the addition of NaSCN enhanced nitric oxide production and oxygen consumption. A different pattern of nitric oxide production was seen with the dietary phenolics compared with ascorbic acid. In addition, two different patterns of nitric oxide response were seen with ferulic acid and caffeic acid and another with gallic acid and chlorogenic acid. Ferulic and caffeic acids produced only a small initial increase in nitric oxide, which was not sustained under either aerobic or anaerobic conditions. In contrast, gallic and chlorogenic acids produced a much more marked rise in nitric oxide, which remained elevated under both aerobic and anaerobic conditions. The only phenolic experiment in which an equivalent concentration of nitric oxide to that with ascorbic acid was observed was with high concentration of gallic acid under anaerobic conditions. These studies indicated that nitrite in the simulated GOJ environment is converted to varying extents to nitric oxide and factors influencing this include luminal pH, thiocyanate, oxygen tension and presence of antioxidants. We have also found that the capacity of antioxidants to convert acidified nitrite to nitric oxide varies as does the temporal profile of the nitric oxide concentration generated by them.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Gastric cardia, nitrite, nitric oxide, ascorbic acid, phenolic compounds
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QD Chemistry
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Supervisor's Name: McColl, Professor Kenneth E.L.
Date of Award: 2009
Depositing User: Dr Aziza Elmesmari
Unique ID: glathesis:2009-1230
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Oct 2009
Last Modified: 10 Dec 2012 13:36
URI: http://theses.gla.ac.uk/id/eprint/1230

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