DIFFERENTIAL DEPLETION OF HUMAN RESPIRATORY-TRACT ANTIOXIDANTS IN RESPONSE TO OZONE CHALLENGE

The toxicity of ozone, the major component of photochemical smog, is r elated to its powerful oxidising ability, and many of its deleterious effects are mediated through free radical reactions. As the majority o f ozone oxidation events are thought to be confined to the pulmonary e pithelial lining fluid, we studied the interaction of ozone with a ran ge of small molecular weight antioxidants found within this compartmen t: ascorbic acid (AH(2)), uric acid (UA), and reduced glutathione (GSH ). Epithelial lining fluid obtained as bronchoalveolar lavage (BAL) fl uid, was taken from 16 male subjects and the antioxidant concentration s determined for each subject. BAL fluid samples from nine of these su bjects were then exposed, using an interfacial exposure system, to a r ange (50-1000 ppb) of ozone concentrations. Both AH(2) and UA were con sumed by ozone in a time and ozone concentration dependent manner, wit h 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 howe ver 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 concent ration. We conclude that there is differential depletion of BAL fluid antioxidants, suggesting a reactivity hierarchy toward ozone in human ELF of AH(2) > UA much greater than GSH.