Antioxidant consumption and repletion kinetics in nasal lavage fluid following exposure of healthy human volunteers to ozone

To obtain information on the real-time events occurring within human respir atory tract Lining fluids (RTLFs) during ozone exposure, sequential nasal l avage was performed on 13 human volunteers exposed on separate occasions to 0.2 parts per million O-3 and filtered air (2-h exposures, with intermitte nt exercise). Nasal lavage was performed and blood samples obtained at four time points t hroughout each exposure: pre-exposure (Pre-E), 1 h into exposure (1h-E), im mediately postexposure (0h-PE) and Ih post-exposure (1h-PE), Endobronchial mucosal biopsies were obtained at 1.5 h-post exposure (1.5 h-PE). Nasal RTLF neutrophilia was not apparent during, or 1.5 h after, O-3 exposu re, Furthermore, activation of the pre-existing neutrophil population did n ot occur. Airway permeability was not altered by this O-3 exposure regimen. Sequential ravage resulted in significant washout of RTLF ascorbic acid, r educed 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 displ ay washout kinetics. Of the antioxidants examined, only UA was clearly depl eted by O-3, concentrations, falling by 6.22 mu mol L-1 at 1h-E, compared w ith 1.61 mu mol.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 O-3 exposure was coincident with a small. but s ignificant increase in plasma UA concentration (19.27 (O-3) versus 1.95 mu mol.L-1 (air), p<0.05). These data demonstrate that inhalation of 0.2 parts per million O-3 results in the depletion of nasal respiratory tract lining fluid uric acid and tha t this regional loss of uric acid leads to a small increase in plasma uric acid concentration, Whilst the reaction of uric acid with inspired O-3 may confer protection locally, the role of upper airway uric acid as a sink for inhaled O-3 is not supported by these findings.