title: Effects of amorphous silica coating on cerium oxide nanoparticles induced pulmonary responses.
abstract: Recently cerium compounds have been used in a variety of consumer products, including diesel fuel additives, to increase fuel combustion efficiency and decrease diesel soot emissions. However, cerium oxide (CeO2) nanoparticles have been detected in the exhaust, which raises a health concern. Previous studies have shown that exposure of rats to nanoscale CeO2 by intratracheal instillation (IT) induces sustained pulmonary inflammation and fibrosis. In the present study, male Sprague-Dawley rats were exposed to CeO2 or CeO2 coated with a nano layer of amorphous SiO2 (aSiO2/CeO2) by a single IT and sacrificed at various times post-exposure to assess potential protective effects of the aSiO2 coating. The first acellular bronchoalveolar lavage (BAL) fluid and BAL cells were collected and analyzed from all exposed animals. At the low dose (0.15mg/kg), CeO2 but not aSiO2/CeO2 exposure induced inflammation. However, at the higher doses, both particles induced a dose-related inflammation, cytotoxicity, inflammatory cytokines, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP at 1day post-exposure. Morphological analysis of lung showed an increased inflammation, surfactant and collagen fibers after CeO2 (high dose at 3.5mg/kg) treatment at 28days post-exposure. aSiO2 coating significantly reduced CeO2-induced inflammatory responses in the airspace and appeared to attenuate phospholipidosis and fibrosis. Energy dispersive X-ray spectroscopy analysis showed Ce and phosphorous (P) in all particle-exposed lungs, whereas Si was only detected in aSiO2/CeO2-exposed lungs up to 3days after exposure, suggesting that aSiO2 dissolved off the CeO2 core, and some of the CeO2 was transformed to CePO4 with time. These results demonstrate that aSiO2 coating reduce CeO2-induced inflammation, phospholipidosis and fibrosis.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA. Electronic address: jym1@cdc.gov.
authors.forename: Jane
authors.initials: J
authors.lastname: Ma
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Barger
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.affiliation: Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Cohen
authors.affiliation: Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
authors.affiliation: School of Pharmacy, West Virginia University, Morgantown, WV, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002563:Cerium / Q000737:chemistry / Q000633:toxicity*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry / Q000494:pharmacology*; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010743:Phospholipids; D037661:Pulmonary Surfactant-Associated Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D002563:Cerium; C030583:ceric oxide; D012822:Silicon Dioxide; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Cerium oxide, amorphous silica; Lung inflammation; Pulmonary fibrosis; Safer by design