Induction of pulmonary fibrosis by cerium oxide nanoparticles

Details

• Personal Author:
  Barger M ; Castranova, Vincent ; Ma JK ; Ma JY ; Mercer RR ; Scabilloni J ; Schwegler-Berry D
• Description:
  Cerium compounds have been used as a diesel engine catalyst to lower the mass of diesel exhaust particles, but are emitted as cerium oxide (CeO(2)) nanoparticles in the diesel exhaust. In a previous study, we have demonstrated a wide range of CeO(2)-induced lung responses including sustained pulmonary inflammation and cellular signaling that could lead to pulmonary fibrosis. In this study, we investigated the fibrogenic responses induced by CeO(2) in a rat model at various time points up to 84 days post-exposure. Male Sprague Dawley rats were exposed to CeO(2) by a single intratracheal instillation. Alveolar macrophages (AM) were isolated by bronchial alveolar lavage (BAL). AM-mediated cellular responses, osteopontin (OPN) and transform growth factor (TGF)-beta1 in the fibrotic process were investigated. The results showed that CeO(2) exposure significantly increased fibrotic cytokine TGF-beta1 and OPN production by AM above controls. The collagen degradation enzymes, metrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitor of MMP were markedly increased in the BAL fluid at 1day- and subsequently declined at 28 days after exposure, but remained much higher than the controls. CeO(2) induced elevated phospholipids in BAL fluid and increased hydrooxyproline content in lung tissue in a dose- and time-dependent manner. Immunohistochemical analysis showed MMP-2, MMP-9 and MMP-10 expressions in fibrotic regions. Morphological analysis noted collagen fibers in the lungs exposed to a single dose of 3.5mg/kg CeO(2) and sacrificed at 28 days post-exposure. Collectively, our studies show that CeO(2) induced fibrotic lung injury in rats, suggesting it may cause potential health effects. [Description provided by NIOSH]
• Subjects:
  Environmental Monitoring Fibrosis Histocytochemistry Immune System Laboratories Lipids Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Vehicle Emissions

  More +
• Keywords:
  Alveolar-cells Author Keywords: Cerium Oxide Biological-effects Cellular-reactions Cerium-compounds Cytochemistry Diesel-emissions Diesel-exhausts Dose-response Exposure-assessment Fibrogenicity Histochemical-analysis Immune-reaction Laboratory-animals Laboratory-testing Lung-disorders Lung-fibrosis Lung-tissue Metalloproteinases Metalloproteins Nanoparticle Nanotechnology Phospholipidosis Phospholipids Pulmonary-system-disorders Pulmonary Fibrosis Respiratory-system-disorders

  More +
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  255-264
• Volume:
  262
• Issue:
  3
• NIOSHTIC Number:
  nn:20040844
• Citation:
  Toxicol Appl Pharmacol 2012 Aug; 262(3):255-264
• Contact Point Address:
  Jane Y. Ma, PPRB/HELD, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505-2888, USA
• Email:
  jym1@cdc.gov
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Transportation, Warehousing and Utilities
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4b4e8ca8545067641276913e4a29ff9960930c143dd55001dca41b1a859537f89931328c710f7e95881b9c513e4f41e813282d68dedb71ba0ae6d62c587a5d97
• Download URL:
  https://stacks.cdc.gov/view/cdc/193563/cdc_193563_DS1.pdf
• File Type:
  [PDF - 1.39 MB ]