title: Antioxidant consumption and repletion kinetics in nasal lavage fluid following exposure of healthy human volunteers to ozone.
abstract: To obtain information on the real-time events occurring within human respiratory tract lining fluids (RTLFs) during ozone exposure, sequential nasal lavage was performed on 13 human volunteers exposed on separate occasions to 0.2 parts per million O3 and filtered air (2-h exposures, with intermittent exercise). Nasal lavage was performed and blood samples obtained at four time points throughout each exposure: pre-exposure (Pre-E), 1 h into exposure (1h-E), immediately post-exposure (0h-PE) and 1 h post-exposure (1h-PE). Endobronchial mucosal biopsies were obtained at 1.5 h-post exposure (1.5h-PE). Nasal RTLF neutrophilia was not apparent during, or 1.5 h after, 03 exposure. Furthermore, activation of the pre-existing neutrophil population did not occur. Airway permeability was not altered by this 03 exposure regimen. Sequential lavage resulted in significant washout of RTLF ascorbic acid, reduced glutathione, extracellular superoxide dismutase and myeloperoxidase at 1h-E, 0h-PE and 1.5h-PE relative to baseline Pre-E values. In contrast, RTLF uric acid (UA), total protein and albumin concentrations did not display washout kinetics. Of the antioxidants examined, only UA was clearly depleted by 03, concentrations, falling by 6.22 micromol x L(-1) at 1h-E, compared with 1.61 micromol x L(-1) (p<0.01) during control air exposure. The establishment of a new pseudo-steady-state concentration of RTLF UA (70% of Pre-E values) during the second hour of O3 exposure was coincident with a small but significant increase in plasma UA concentration (19.27 (O3) versus 1.95 micromol x L(-1) (air), p<0.05). These data demonstrate that inhalation of 0.2 parts per million 03 results in the depletion of nasal respiratory tract lining fluid uric acid and that this regional loss of uric acid leads to a small increase in plasma uric acid concentration. Whilst the reaction of uric acid with inspired 03 may confer protection locally, the role of upper airway uric acid as a sink for inhaled O3 is not supported by these findings.
authors.affiliation: Lung Biology, Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: I S
authors.initials: IS
authors.lastname: Mudway
authors.forename: A
authors.initials: A
authors.lastname: Blomberg
authors.forename: A J
authors.initials: AJ
authors.lastname: Frew
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: T
authors.initials: T
authors.lastname: Sandström
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000418:Albumins / Q000032:analysis; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000032:analysis; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D018592:Cross-Over Studies; D005260:Female; D005978:Glutathione / Q000032:analysis; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000473:pathology; D017817:Nasal Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D018384:Oxidative Stress; D010126:Ozone / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis; D011506:Proteins / Q000032:analysis; D016037:Single-Blind Method; D013482:Superoxide Dismutase / Q000032:analysis; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000418:Albumins; D000975:Antioxidants; D010083:Oxidants, Photochemical; D011506:Proteins; D014527:Uric Acid; D010126:Ozone; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid