This work investigated the role of nasal lining fluid (NLF) uric acid in modulating O3 absorption in the human nasal cavity. Ozone absorption was measured as the fractional uptake (Λ) of O 3 from a humidified air stream containing 0.36 parts per million (ppm) O3, and flowing through the nose unidirectionally at 3 liters per minute (1pm). Contents of the NLF were sampled by nasal lavage with saline. Previous studies report that a relationship between daily measurements of Λ and uric acid (UA) concentration in the NLF (CUA,NLF) cannot be observed due to significant day-to-day variations in parameters affecting Λ. To overcome this problem, several perturbations were imposed to induce changes in CUA,NLF, and therefore Λ, allowing same-day comparison of these parameters.; In a preliminary study, we investigated the effect of continuous O 3 exposure on Λ in fifteen subjects. It was hypothesized that O3 exposure would temporarily deplete CUA,NLF, resulting in lowered Λ. Results showed that Λ was significantly reduced (p0.001) following exposure to 0.36 ppm O3 for 30 minutes at 3 1pm. In a subsequent study of twenty-five subjects, we aimed to relate values of Λ and CUA,NLF before and after O3 exposure. Values of Λ and CUA,NLF were significantly reduced following O3 exposure and were strongly correlated with each other (p0.001). Regression of these data indicated that Λ=0 when CUA,NLF=0, suggesting a major contribution of UA in modulating O3 uptake.; In a third study, we investigated effects of the oxidant gas nitrogen dioxide (NO2) on Λ in twelve subjects. Exposure to 1.0 ppm NO2 at 3 1pm for 30 minutes resulted in a small reduction of Λ, and no change in CUA. Results of in vitro experiments verified minimal reactivity between gaseous NO2 and UA in aqueous solution. Therefore, the facts that (1) CUA,NLF was not influenced by NO2 exposure and (2) NO2 exposure induced only a small reduction in Λ, are in agreement with the assumption that UA is the major NLF target of O3.; Analysis of data from a previous study (Santiago, 2001) that employed serial nasal lavages to dilute UA levels in NLF showed a strong correlation (p0.001) between values of CUA and the corresponding Λ values at each sampling time. The results of this analysis indicated that there can be O3 transport in the absence of UA, likely due to oxidation of exposed cell membranes following serial nasal lavage challenges.; A concentration profile for O3 in the NLF was simulated with the reaction-diffusion model employing a value for k2=10 9 M-1s-1 and CUA,NLF=200 muM. We attempted to detect secondary products of O3 oxidation, such as lipid peroxides and aldehydes, that might explain how O3 exposure causes adverse health effects. Results demonstrated significant production of TBARS, a marker of lipid peroxidation, immediately following and 60 minutes following O3 exposure. Interestingly, increased levels of C UA,NLF appeared to reduce absolute TBARS formation, suggesting a secondary protective role for UA.; Increased cellular production of gaseous nitric oxide (NO) has been implicated during inflammation. Therefore, in the first study, nasal air was monitored before and after O3 exposure as an indicator of an inflammatory response to O3. Our data showed a small, but significant elevation of NO one hour following initiation of O3 exposure, suggesting an emerging inflammatory response. (Abstract shortened by UMI.)
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