Detection of aldehydes in bronchoalveolar lavage of rats exposed to ozone

We report the detection of hexanal, heptanal, and nonanal in the bronchoalveolar lavage (BAL) of rats exposed to 0.5 to 10 ppm ozone with or without simultaneous 5% CO2. These three aldehydes primarily result from the Criegee ozonation of specific mono- or polyunsaturated fatty acids that are present in significant amounts in the rat lung; e.g., palmitoleic acid gives heptanal, oleic gives nonanal, and linoleic and arachidonic can give hexanal. Hexanal also is produced in the ozone-initiated autoxidation of any n-6 polyunsaturated fatty acid, and thus is a measure of generalized oxidative stress. (Monounsaturated fatty acids do not undergo appreciable autoxidation.) This detection and quantitation of aldehydes directly demonstrates for the first time that unsaturated fatty acids undergo Criegee ozonation in the lung when ozone is inhaled. Exposure to ozone alone produced smaller apparent yields of the three aldehydes than did exposure to ozone plus 5% CO2. Hexanal, heptanal, and nonanal can be detected in BAL of rats 5 hr after the end of the ozone exposure, but after more than 5 hr only hexanal can be found, probably from ozone-induced autoxidation of n-6 PUFA that continues after ozone exposure. The measured amounts of aldehydes are low, and that, coupled with inherent biovariability, suggests that aldehydes may not be useful as quantitative dosimeters. However, they can be useful biomarkers, since some of these aldehydes (e.g., nonanal) are produced in ozone-specific pathways and aldehydes are the most easily detected among the lipid ozonation products (LOP). Furthermore, our identification of these aldehydes by BAL, coupled with our recognition that ozone itself cannot penetrate far enough into the lung to cause many of the effects associated with the inhalation of ozone, suggests that these aldehydes, as well as other types of LOP (such as hydroxyhydroperoxides and Criegee ozonides), may act as signal transduction molecules, activating lipases and causing the release of inflammatory molecules by a variety of pathways not yet entirely elucidated.