Pryor W A, Bermúdez E, Cueto R, Squadrito G L
Biodynamics Institute, Louisiana State University, Baton Rouge 70803-1800, USA.
Fundam Appl Toxicol. 1996 Nov;34(1):148-56. doi: 10.1006/faat.1996.0185.
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.
我们报告了在暴露于0.5至10 ppm臭氧（有无同时存在5%二氧化碳）的大鼠支气管肺泡灌洗（BAL）中检测到己醛、庚醛和壬醛。这三种醛主要源于大鼠肺中大量存在的特定单不饱和或多不饱和脂肪酸的克里格臭氧氧化反应；例如，棕榈油酸生成庚醛，油酸生成壬醛，亚油酸和花生四烯酸可生成己醛。己醛也可在任何n-6多不饱和脂肪酸的臭氧引发的自氧化过程中产生，因此是全身性氧化应激的一个指标。（单不饱和脂肪酸不会发生明显的自氧化反应。）醛类的这种检测和定量首次直接证明，吸入臭氧时不饱和脂肪酸在肺中会发生克里格臭氧氧化反应。单独暴露于臭氧时，这三种醛的表观产率低于暴露于臭氧加5%二氧化碳时。在臭氧暴露结束后5小时，可在大鼠的BAL中检测到己醛、庚醛和壬醛，但5小时后只能检测到己醛，这可能是由于臭氧暴露后n-6多不饱和脂肪酸的臭氧诱导自氧化仍在继续。所测得的醛含量很低，再加上固有的生物变异性，表明醛类可能不太适合用作定量剂量计。然而，它们可以作为有用的生物标志物，因为其中一些醛（如壬醛）是通过臭氧特异性途径产生的，而且醛类是脂质臭氧氧化产物（LOP）中最容易检测到的。此外，我们通过BAL对这些醛的鉴定，以及我们认识到臭氧本身无法深入肺内足够远的距离以引发许多与吸入臭氧相关的效应，这表明这些醛以及其他类型的LOP（如羟基氢过氧化物和克里格臭氧化物）可能作为信号转导分子，通过尚未完全阐明的多种途径激活脂肪酶并导致炎症分子的释放。
