title: In vivo salicylate hydroxylation: a potential biomarker for assessing acute ozone exposure and effects in humans.
abstract: Ozone is known to yield hydroxyl radical, which may contribute to ozone-mediated lung injury. In the presence of hydroxyl radical, salicylate is hydroxylated to form 2,3-dihydroxybenzoic acid (2,3-DHBA). There is no evidence of enzymatic formation of 2,3-DHBA. We hypothesized that salicylate hydroxylation might be used as a biomarker indicating human exposure to ozone. Healthy, nonsmoking volunteers, 18 to 34 yr of age, were given acetylsalicylic acid (975 mg) or placebo orally 0.5 h before an exposure. Subjects were exposed to ozone (0.12 or 0.4 ppm) or filtered air in an environmental chamber for 2 h, while performing intermittent exercise. Results indicate significant decrements in FVC, FEV1.0, forced expiratory flows at 50% and 75% of FVC, and peak expiratory flow rate, and an increase in airway resistance, after exposure to 0.4 ppm ozone in comparison with air control (p < 0.05). Exposure to 0.4 ppm ozone also resulted in increased symptom numbers and severity (p < 0.05). When subjects were exposed to 0.12 ppm ozone, changes of pulmonary function and symptoms reported were minimal. Plasma concentration of 2,3-DHBA was significantly increased after exposure to 0.12 and 0.4 ppm ozone in comparison with air control (p < 0.05). There was a significant correlation between ozone-induced changes of pulmonary function and normalized salicylate hydroxylation (p < 0.05). The results indicate that exposure to ozone can initiate in vivo production of hydroxyl radical, a potent reactive agent. Salicylate hydroxylation may then serve as a sensitive dosimetric biomarker for ozone exposure, even at subclinical ozone exposure levels.
authors.affiliation: Air Quality Health Effects Research Section, Environmental Health Directorate, Health Canada, Ottawa, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J A
authors.initials: JA
authors.lastname: Leech
authors.forename: R B
authors.initials: RB
authors.lastname: Urch
authors.forename: F S
authors.initials: FS
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001241:Aspirin / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D062385:Hydroxybenzoates / Q000097:blood; D006900:Hydroxylation; D019570:Inhalation Exposure; D016210:Methacholine Chloride; D010126:Ozone / Q000009:adverse effects*; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D015415:Biomarkers; D016085:Bronchoconstrictor Agents; D062385:Hydroxybenzoates; D016210:Methacholine Chloride; D010126:Ozone; C009135:2,3-dihydroxybenzoic acid; D001241:Aspirin