title: Investigation of the effects of short-term inhalation of carbon nanoparticles on brains and lungs of c57bl/6j and p47(phox-/-) mice.
abstract: Recent studies indicate that the brain is a target for toxic carbonaceous nanoparticles present in ambient air. It has been proposed that the neurotoxic effects of such particles are driven by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated generation of reactive oxygen species (ROS) in activated microglia. In the present study, we have evaluated the effects of short term (4h) nose-only inhalation exposure to carbon NP (CNP) in the brains and lungs of C57BL/6J mice and in p47(phox-/-) mice that lack a functional NADPH oxidase. It was shown that the lungs of the p47(phox-/-) mice are less responsive to CNP inhalation than lungs of the corresponding C57BL/6J control animals. Lung tissue mRNA expression of the oxidative stress/DNA damage response genes 8-oxoguanine glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 (APE1) were induced by CNP exposure in C57BL/6J but not in the p47(phox-/-) mice. In contrast, the expression of these genes, as well as Tumor Necrosis Factor-α (TNFα), Cyclooxygenase-2 (COX-2) and Heme Oxygenase-1 (HO-1) was not altered in the olfactory bulb, cerebellum or remaining brain tissue part of either mouse background. This indicates that neuroinflammation was not induced by this exposure. CNP inhalation for 4h or for 4h on three consecutive days also did not affect brain tissue protein expression of interleukin (IL)-1β, while a clear significant difference in constitutive expression level of this pro-inflammatory cytokine was found between C57BL/6J and p47(phox-/-) mice. In conclusion, short-term inhalation exposure to pure carbon nanoparticles can trigger mild p47(phox) dependent oxidative stress responses in the lungs of mice whereas in their brains at the same exposure levels signs of oxidative stress and inflammation remain absent. The possible role of p47(phox) in the neuro-inflammatory effects of nanoparticles in vivo remains to be clarified.
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: D
authors.initials: D
authors.lastname: van Berlo
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hullmann
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wessels
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Scherbart
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: F R
authors.initials: FR
authors.lastname: Cassee
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Gerlofs-Nijland
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Albrecht
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany. Electronic address: roel.schins@uni-duesseldorf.de.
authors.forename: R P F
authors.initials: RPF
authors.lastname: Schins
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002244:Carbon / Q000008:administration & dosage*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D045647:DNA Glycosylases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002244:Carbon; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse
keywords: Carbon nanoparticles; Inflammation; NADPH oxidase; Oxidative stress