Journal Article

PreJuSER-10235

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain

van Berlo, D. ; Albrecht, C. ; Knaapen, A. ; Flemming, R. C. ; Gerlofs-Nijland, M. E. ; Kooter, I. M. ; Palomero-Gallagher, N.FZJ* ; Bidmon, H.-J. ; van Schooten, F.-J. ; Krutmann, J. ; Schins, R. P. F.

2010
Springer Berlin

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Please use a persistent id in citations: doi:10.1007/s00204-010-0551-7

Abstract: 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.

Keyword(s): J ; Diesel engine exhaust (auto) ; Nanoparticles (auto) ; Brain (auto) ; Oxidative stress (auto) ; CYP1A1 (auto) ; Heme oxygenase-1 (auto)

Note: We thank the members of the Dutch National Vaccine Institute and RIVM, especially John Boere, Daan Leseman and Paul Fokkens, for their experimental assistance. This study is supported by grants from the German Federal Ministry of Environment (BMU), and RIVM, Netherlands (S630111). Sponsors did not participate in study design; collection, analysis, and interpretation of data; and writing of the manuscript.

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (FUEK409) (FUEK409)
2. 89571 - Connectivity and Activity (POF2-89571) (POF2-89571)

Appears in the scientific report 2010

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