title: Differential depletion of human respiratory tract antioxidants in response to ozone challenge.
abstract: The toxicity of ozone, the major component of photochemical smog, is related to its powerful oxidising ability, and many of its deleterious effects are mediated through free radical reactions. As the majority of ozone oxidation events are thought to be confined to the pulmonary epithelial lining fluid, we studied the interaction of ozone with a range of small molecular weight antioxidants found within this compartment: ascorbic acid (AH2), uric acid (UA), and reduced glutathione (GSH). Epithelial lining fluid obtained as bronchoalveolar lavage (BAL) fluid, was taken from 16 male subjects and the antioxidant concentrations determined for each subject. BAL fluid samples from nine of these subjects were then exposed, using an interfacial exposure system, to a range (50-1000 ppb) of ozone concentrations. Both AH2 and UA were consumed by ozone in a time and ozone concentration dependent manner, with mean consumption rates of 1.7 +/- 0.8 and 1.0 +/- 0.5 pmol L-1 s-1 ppb-1, respectively. Considerable intersubject variation was however observed. The individual rates of consumption for each antioxidant were significantly correlated with the respective initial antioxidant concentration. In contrast, although GSH was consumed at 50 ppb ozone, the rate of consumption did not change with increasing ozone concentration. We conclude that there is differential depletion of BAL fluid antioxidants, suggesting a reactivity hierarchy toward ozone in human ELF of AH2 > UA > > GSH.
authors.affiliation: Rayne Institute, St Thomas' Hospital, London.
authors.forename: I S
authors.initials: IS
authors.lastname: Mudway
authors.forename: D
authors.initials: D
authors.lastname: Housley
authors.forename: R
authors.initials: R
authors.lastname: Eccles
authors.forename: R J
authors.initials: RJ
authors.lastname: Richards
authors.forename: A K
authors.initials: AK
authors.lastname: Datta
authors.forename: T D
authors.initials: TD
authors.lastname: Tetley
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010084:Oxidation-Reduction; D010126:Ozone / Q000633:toxicity*; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010083:Oxidants, Photochemical; D014527:Uric Acid; D010126:Ozone; D005978:Glutathione; D001205:Ascorbic Acid