Effects of the physicochemical properties of nano-scaled cerium oxide on fibrogenesis

Details

• Personal Author:
  Barger M ; Davidson DC ; Demokritou P ; Derk R ; Ma JY ; Stueckle, Todd A. ; Wang L
• Description:
  Nano-scaled cerium oxide (nCeO2) is used in a variety of applications, including use as a fuel additive, catalyst, and polishing agent, yet potential adverse health effects associated with nCeO2 exposure remain incompletely understood. In vivo studies have shown in a rat model that inhaled nCeO2 can deposit in deep lung tissues and induce fibrosis; however, little is known about how the physicochemical properties of nCeO2, such as size or surface chemistry (e.g. amorphous silica coating), may affect the bio-activity of these particles. Thus, we hypothesized that the physicochemical properties of nCeO2 influence its fibrogenicity. Plasma samples collected from rats 28 days after intratracheal instillation of 3.5 mg/kg nCeO2 showed increased levels of the fibrotic mediator TGFbeta, which is released from macrophages and platelets upon stimulation. This was not observed in response to amorphous silica-coated nCeO2 (amsCeO2), which induced levels consistent with saline-treated animals. Interestingly, platelets isolated from nCeO2-treated rats released significantly more TGFbeta than those isolated from control animals, suggesting that platelets may be contributing to nCeO2-induced fibrosis. This was found to be an indirect effect since treatment of control platelets ex vivo did not stimulate release of TGFbeta, regardless of the size or coating of nCeO2. Primary alveolar macrophages demonstrated increased cell death when treated with nCeO2, but not amsCeO2, at doses consistent with those used in vivo, while neither particle directly induced TGFbeta release from these cells. Furthermore, nCeO2 directly induced the production of collagen I and increased cell proliferation, hallmarks of fibrogenesis, in primary lung fibroblasts in vitro, while amsCeO2 failed to do so to the same extent. Collectively, these results indicate that differences in the physicochemical properties of nCeO2 may affect the fibrogenicity of this compound, and highlight the utility of "safe-by-design" strategies for preparing engineered nanomaterials. [Description provided by NIOSH]
• Subjects:
  Chemistry Laboratories Lung Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Alveolar-cells Bioactivation Cell-damage Cellular-reactions Cerium-compounds Chemical-properties Coatings Dose-response Fibrogenesis Fibrogenicity Laboratory-animals Laboratory-testing Lung-cells Lung-fibrosis Nanotechnology Physical-properties Physiological-chemistry Platelets Surface-properties

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 9 ; 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:
  64
• Volume:
  144
• Issue:
  1
• NIOSHTIC Number:
  nn:20045886
• Citation:
  Toxicologist 2015 Mar; 144(1):64
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3) ; Silica (CAS RN 7631-86-9)
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9fd9baeac2f4533ac40c8c50c8857e11ec50375a63b0b3aac6c7fa15b74af0c3e8e13da93d8e4a06d68bef4898f11939bd48fb4c8bbd3d7a4517c1f2defa3023
• Download URL:
  https://stacks.cdc.gov/view/cdc/201134/cdc_201134_DS1.pdf
• File Type:
  [PDF - 227.62 KB ]