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Title: Investigating the relative toxicity of nitrogen dioxide in a human respiratory tract lining fluid model
Author: Katsaiti, Irene Natali
ISNI:       0000 0004 5350 2346
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2014
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Epidemiological studies have shown that long term exposure to ozone (O3), nitrogen dioxide (NO2) and particulate matter (PM) are associated with adverse effects on lung function. However, disentangling the independent effects of each pollutant has proved difficult, if not an impossible task. Toxicological evidence is necessary, but no experimental study so far has compared the oxidative effects of these three air pollutants under the same controlled conditions. Air pollutants are believed to cause their pathophysiological actions in the respiratory system, at least in part, through oxidative stress. The principal objective of this study was to assess their order of significance by measuring their oxidative potential in our respiratory tract lining fluid model. Synthetic respiratory tract lining fluid (synRTLF) was exposed to varying O3 and NO2 concentrations (0, 50, 150, 400, 1000 ppb) for 120 minutes. Aliquots of synRTLF were removed from the exposure chamber every 30 minutes and the concentrations of ascorbate, urate, and glutathione (reduced and oxidised) were measured. Similarly, filter disc cuts of PM collected daily from roadside and background locations in London, were incubated in synRTLF. The quantification methods used were the same as those used for the gaseous exposures. These experimental findings constitute the first to compare the effects of O3 and NO2 in a lung lining fluid model under the same experimental conditions. O3 caused significantly greater antioxidant depletion than NO2 in vitro. Direct comparison of the antioxidant depletion actions of the three air pollutants was achieved by applying the experimentally calculated rates on the pollutant’s daily mean concentrations. The results revealed that (on the days considered) PM was responsible for higher antioxidant depletion across all tested days and sites when compared with the gases. The higher levels of NO2 at roadside compared with O3 at the same location resulted in a significantly higher overall oxidative capacity of NO2 compared with O3 at roadside, while the opposite effect was observed at the background London site. All three air pollutants considered resulted in antioxidant depletion in our lung lining fluid model, and thus our findings offer further support that the antioxidants in the respiratory system are playing a protective role. Also, these results highlighted the oxidative potential of PM and the significance of NO2 exposure at roadside locations.
Supervisor: Kelly, Frank James; Walton, Heather Anne Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available