Effects of combined exposure to diesel exhaust particles and cerium oxide nanoparticles on the response to endotoxin in rats

Details

• Personal Author:
  Barger MW ; Castranova, Vincent ; Dolash BD ; Ma JY
• Description:
  Cerium compounds have been used as diesel fuel catalysts to lower the burn-off temperature of diesel exhaust particles (DEP). This catalysis increases the lifetime and efficiency of exhaust filters and lowers DEP emissions; however results in cerium oxide nanoparticles (CNP) released in the exhaust. Previous studies from our laboratory have shown that DEP and/or CNP induced lung inflammation, damage and fibrosis. This study focuses on the effects of DEP- and/or CNP-exposed rats on the susceptibility to endotoxin. Male Sprague-Dawley rats were treated by intratracheal (IT) instillation of DEP (5 mg/kg body weight) and/or CNP (1 mg/kg body weight). After 3 days, the rats were exposed to lipopolysaccharide (LPS) by IT instillation (1 mg/kg body weight) and then sacrificed after 3 additional days. CNP, DEP and CNP+DEP exposures induced neutrophilia, enlarged macrophages, and released inflammatory mediators, interleukin-12 (IL-12) and osteopontin (OPN), into the bronchial alveolar lavage (BAL) fluid. The exposure to LPS further increased neutrophilia, but did not affect particle-induced cytotoxicity and air/capillary damage. LPS exposure did not affect IL-12 and OPN production in rats treated with DEP or CNP+DEP, but significantly increased IL-12 and OPN in BAL fluid of CNP-treated rats. Increased transforming growth factor beta (TGF-beta), an important mediator of fibrosis detected in alveolar macrophages isolated from all particle-exposed rats. TGF-beta induction was further enhanced in response to LPS. A significant increase in matrix metalloproteinase-9 (MMP-9) was seen in BAL from CNP- and CNP+DEP-exposed rats. Tissue inhibitor of metalloproteinase 1 (TIMP-1), a MMP-9 inhibitor, was markedly increased in particle-exposed groups. LPS exposure did not significantly alter particles-induced MMP-9, but markedly enhanced TIMP-1 levels. These results suggest endotoxin exposure significantly increased TGF-beta production, but lowered the MMP-9/TIMP-1 ratio. These changes may lead to extracellular matrix damage and fibrotic development, leading to health concerns. [Description provided by NIOSH]
• Subjects:
  Environmental Monitoring Immune System Laboratories Lung Occupational Health Particulate Matter Respiratory System Safety Vehicle Emissions
• Keywords:
  Cerium-compounds Diesel-exhausts Dose-response Exposure-assessment Exposure-levels Exposure-methods Heart Immune-reaction Laboratory-animals Laboratory-techniques Laboratory-testing Nanotechnology Particulates Pulmonary-system Vasoactive-agents

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; 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:
  69
• Volume:
  126
• NIOSHTIC Number:
  nn:20040578
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):69
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3) ; Cerium (CAS RN 7440-45-1)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Transportation, Warehousing and Utilities
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fbeaa1cff0d6d9ba1b1e678a17fc67160932a23203e90cdce2a003f7879417e26f8a2fe7f8084c8ed49168805a4800aca355e18ab8d50844e0e6c32cab5cd1a4
• Download URL:
  https://stacks.cdc.gov/view/cdc/193381/cdc_193381_DS1.pdf
• File Type:
  [PDF - 475.96 KB ]