Oxidants, antioxidants, and respiratory tract lining fluids.

Cross, Carroll E.; Vliet, Albert van der; O’Neill, Charles; Louie, Samuel; Halliwell, Barry

doi:10.1289/ehp.94102s10185

Cited by 222 publications

(76 citation statements)

References 84 publications

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“…The thiol containing antioxidants glutathione and albumin are found in high concentrations in the ELF27 and are nitrosated by NO redox equivalents (N 2 O 3 and N 2 O 4 ) to produce S-nitrosothiols (RS-NO) 26…”

Section: Discussionmentioning

confidence: 99%

Acute inhalation of cigarette smoke increases lower respiratory tract nitric oxide concentrations

Chambers

Tunnicliffe

Ayres

1998

Thorax

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Background-Cigarette smoking is associated with a number of common pulmonary diseases including chronic airflow limitation and bronchial carcinoma. Lower respiratory tract (LRT) nitric oxide (NO) concentrations are reduced in habitual cigarette smokers between cigarettes, and although this finding has been implicated in the pathogenesis of smoking related disease, the underlying mechanisms are unclear. A study was undertaken to determine the nature and time course for changes in LRT NO concentrations following acute inhalation of cigarette smoke. Methods-Twenty four healthy habitual smokers were studied. The concentration of LRT NO in exhaled breath before, one and ten minutes after smoking a single cigarette was measured using chemiluminescence. Results-LRT NO concentrations increased in all subjects from a mean (SE) of 2.6 (0.27) to 4.8 (0.26) ppb (p<0.0001) at one minute, and at 10 minutes remained significantly raised above the baseline level at 3.2 (0.25) ppb (p = 0.003). The mean (95% CI) increases in NO concentrations were 2.2 (1.7 to 2.7) and 0.6 (0.2 to 1.0) ppb, respectively. Conclusions-These findings were unexpected in both their direction and time course. They suggest a novel mechanism for the handling of NO in the human lung. We hypothesise that NO is trapped in the epithelial lining fluid (ELF) of the normal human respiratory tract in bioequivalent forms such as S-nitrosothiols or peroxynitrite and that this trapping mechanism is sensitive to the redox state of the ELF. LRT NO concentrations will thus increase with oxidant exposure and decline as pulmonary antioxidant defence mechanisms take eVect. These findings may have implications for the pathogenesis and diagnosis of oxidant mediated pulmonary disease. (Thorax 1998;53:677-679)

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Section: Discussionmentioning

confidence: 99%

Acute inhalation of cigarette smoke increases lower respiratory tract nitric oxide concentrations

Chambers

Tunnicliffe

Ayres

1998

Thorax

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“…Numerous human, animal, and vegetation studies have shown that the first line of defense against any oxidative challenge is mobilization of antioxidants (Heath et al, 2009;Samet et al, 2001;Schelegle et al, 2007). For example, O 3 reacts with ascorbic acid, reduced glutathione, and uric acid antioxidants contained in the human epithelial lining fluid (ELF) that scavenge free (Avissar et al, 2000;Ballinger et al, 2005;Cross et al, 1994;Mudway et al, 1996;Samet et al, 2001).…”

Section: Induction Phase Responsementioning

confidence: 99%

An alternative form and level of the human health ozone standard

Lefohn¹,

Hazucha²,

Shadwick³

et al. 2010

Inhalation Toxicology

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Controlled human laboratory studies have shown that there is a disproportionately greater pulmonary function response from higher hourly average ozone (O3) concentrations than from lower hourly average values and thus, a nonlinear relationship exists between O3 dose and pulmonary function (FEV1) response. The nonlinear dose-response relationship affects the efficacy of the current 8-h O3 standard to describe adequately the observed spirometric response to typical diurnal O3 exposure patterns. We have reanalyzed data from five controlled human response to O3 health laboratory experiments as reported by Hazucha et al. (1992), Adams (2003, 2006a, 2006b), and Schelegle et al. (2009). These investigators exposed subjects to multi-hour variable/stepwise O3 concentration profiles that mimicked typical diurnal patterns of ambient O3 concentrations. Our findings indicate a common response pattern across most of the studies that provides valuable information for the development of a lung function (FEV1)-based alternate form for the O3 standard. Based on our reanalysis of the realistic exposure profiles used in these experiments, we suggest that an alternative form of the human health standard, similar to the proposed secondary (i.e., vegetation) standard form, be considered. The suggested form is an adjusted 5-h cumulative concentration weighted O3 exposure index, which addresses both the delay associated with the onset of response (FEV1 decrement) and the nonlinearity of response (i.e., the greater effect of higher concentrations over the mid- and low-range values) on an hourly basis.

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“…These findings provide the first evidence that GSA is formed in vivo. The assay was sufficiently sensitive to detect GSA in samples collected by a lavage process that typically gives ∼100-fold dilution of the epithelial lining fluid [42]. Based on this dilution factor, actual GSA concentrations could be several hundred nanomolar.…”

Section: Analysis Of Biological Samplesmentioning

confidence: 99%