Wa. Pryor et al., DETECTION OF ALDEHYDES IN BRONCHOALVEOLAR LAVAGE OF RATS EXPOSED TO OZONE, Fundamental and applied toxicology, 34(1), 1996, pp. 148-156
We report the detection of hexanal, heptanal, and nonanal in the bronc
hoalveolar lavage (BAL) of rats exposed to 0.5 to 10 ppm ozone with or
without simultaneous 5% CO2. These three aldehydes primarily result f
rom the Criegee ozonation of specific mono- or polyunsaturated fatty a
cids that are present in significant amounts in the rat lung; e.g., pa
lmitoleic acid gives heptanal, oleic gives nonanal, and linoleic and a
rachidonic can give hexanal. Hexanal also is produced in the ozone-ini
tiated autoxidation of any n-6 polyunsaturated fatty acid, and thus is
a measure of generalized oxidative stress. (Monounsaturated fatty aci
ds do not undergo appreciable autoxidation.) This detection and quanti
tation of aldehydes directly demonstrates for the first time that unsa
turated fatty acids undergo Criegee ozonation in the lung when ozone i
s 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 en
d 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 conti
nues after ozone exposure. The measured amounts of aldehydes are low,
and that, coupled with inherent biovariability, suggests that aldehyde
s may not be useful as quantitative dosimeters. However, they can be u
seful biomarkers, since some of these aldehydes (e.g., nonanal) are pr
oduced in ozone-specific pathways and aldehydes are the most easily de
tected among the lipid ozonation products (LOP). Furthermore, our iden
tification of these aldehydes by BAL, coupled with our recognition tha
t 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 hydroxyhydrop
eroxides and Criegee ozonides), may act as signal transduction molecul
es, activating lipases and causing the release of inflammatory molecul
es by a variety of pathways not yet entirely elucidated. (C) 1996 Soci
ety of Toxicology.