title: The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice.
abstract: Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1mg/m(3)), FB1 (6.75mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP-A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE-induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure.
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, Damanhour University, Egypt. Electronic address: dr_hazemshaheen3010@yahoo.com.
authors.forename: Hazem M
authors.initials: HM
authors.lastname: Shaheen
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan; Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, Japan; Research Fellow of Japan Society for the Promotion of Science, Japan. Electronic address: atsutoyukari@gmail.com.
authors.forename: Atsuto
authors.initials: A
authors.lastname: Onoda
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan. Electronic address: shinkai49@gmail.com.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shinkai
authors.affiliation: Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Tokyo University of Science, Japan. Electronic address: m.n.canalcatfish@gmail.com.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan; Department of Pharmacology, Faculty of Veterinary Medicine, South Valley University, Egypt. Electronic address: ashraf_elghoneimy@yahoo.com.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: El-Ghoneimy
authors.affiliation: Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Egypt. Electronic address: yasser_tf@yahoo.com.
authors.forename: Yasser S
authors.initials: YS
authors.lastname: El-Sayed
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan. Electronic address: takedak@rs.noda.tus.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, Japan. Electronic address: masa-ume@rs.noda.tus.ac.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Umezawa
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001991:Bronchitis / Q000209:etiology; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D002518:Ceramides / Q000037:antagonists & inhibitors; D037341:Fumonisins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D002274:Carcinogens, Environmental; D002518:Ceramides; D037341:Fumonisins; D001335:Vehicle Emissions; C056933:fumonisin B1
keywords: Ceramide; Diesel exhaust; Fumonisin B1; Immunohistochemistry; Lung; RT-qPCR