Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain.
Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m(3)), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-alpha, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung.
van Berlo
Damien
D
Institut für Umweltmedizinische Forschung an der Heinrich-Heine-Universität Düsseldorf gGmbH, Düsseldorf, Germany.
Albrecht
Catrin
C
Knaapen
Ad M
AM
Cassee
Flemming R
FR
Gerlofs-Nijland
Miriam E
ME
Kooter
Ingeborg M
IM
Palomero-Gallagher
Nicola
N
Bidmon
Hans-Jürgen
HJ
van Schooten
Frederik-Jan
FJ
Krutmann
Jean
J
Schins
Roel P F
RP
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000494:pharmacology; D019570:Inhalation Exposure; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D001335:Vehicle Emissions / Q000032:analysis*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
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