title: Nanoparticle-rich diesel exhaust-induced liver damage via inhibited transactivation of peroxisome proliferator-activated receptor alpha.
abstract: Diesel exhaust emission contains a high amount of nano-sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been reported. The present investigation focuses on the effects of NR-DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24 ± 7 µg/m3), medium (39 ± 4 µg/m3) and high (138 ± 20 µg/m3) concentrations of NR-DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin-6 and hepatic nuclear factor kappa B (NFκB), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator-activated receptor (PPAR) α levels or its binding activity to the response element, neither activated PPARα-target genes such as β-oxidative enzymes nor inhibited NFκB elevation. Thus, NR-DE may contain some materials that inhibit PPARα activation in relation to lipid metabolism and inflammation. Taken together, NR-DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1985-1995, 2016.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Japan.|Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yanagiba
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Doni Hikmat
authors.initials: DH
authors.lastname: Ramdhan
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Environmental Nanotoxicology Section, Research Center for Environmental Risk, National Institute for Environmental Studies, Ibaraki, Japan.
authors.forename: Akira K
authors.initials: AK
authors.lastname: Suzuki
authors.affiliation: Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D047493:PPAR alpha / Q000378:metabolism*; D010316:Particle Size; D011916:Rats, Inbred F344; D013997:Time Factors; D015533:Transcriptional Activation; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D015850:Interleukin-6; D047493:PPAR alpha; D001335:Vehicle Emissions
keywords: inflammation; lipid metabolism; liver; nanoparticle-rich diesel exhaust; peroxisome proliferator-activated receptor alpha