Cited by 142Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisOccupational and environmental lung diseasesNanoparticles: synthesis and applications

Induction of pulmonary fibrosis by cerium oxide nanoparticles

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Ma, Jane Y., Mercer, Robert R., Barger, Mark, Schwegler-Berry, Diane, Scabilloni, James, Ma, Joseph K., Castranova, Vincent·2012·Toxicology and Applied Pharmacology

Abstract

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)-β1 in the fibrotic process were investigated. The results showed that CeO(2) exposure significantly increased fibrotic cytokine TGF-β1 and OPN production by AM above controls. The collagen degradation enzymes, matrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitor of MMP were markedly increased in the BAL fluid at 1 day- 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 hydroxyproline 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 increased collagen fibers in the lungs exposed to a single dose of 3.5mg/kg CeO(2) and euthanized 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.

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Crossref · 10.1016/j.taap.2012.05.005

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Authors
Ma, J. Y., Mercer, R. R., Barger, M., Schwegler-Berry, D., Scabilloni, J., Ma, J. K., & Castranova, V.
Affiliations
  • National Institute for Occupational Safety and Health (US)
  • West Virginia University (US)
Corresponding author
Ma, Jane Y.
Venue
Toxicology and Applied Pharmacology
Publisher
Elsevier BV
Published
2012-08
Volume
262
Issue
3
Pages
255-264
ISSN
0041-008X (ISSN-L)
OpenAlex
W2098125669
Cited by
142
References
46
Citations by year
2026: 7 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 12 · 2016: 16 · 2015: 18 · 2014: 16 · 2013: 7 · 2012: 2
FWCI
11.09
Type
journal article
Language
en
Open access
Locations
  • Toxicology and Applied Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (CC999999)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
  • Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
Keywords
cerium oxide nanoparticles, pulmonary fibrosis, diesel exhaust particles, alveolar macrophages, TGF-β1, osteopontin, matrix metalloproteinases, MMP-2, MMP-9, MMP-10, tissue inhibitors of metalloproteinases, collagen deposition, hydroxyproline, phospholipids, intratracheal instillation
MeSH terms
Animals, Bronchoalveolar Lavage Fluid, Cerium, Dose-Response Relationship, Drug, Hydroxyproline, Lung, Male, Pulmonary Fibrosis, Macrophages, Alveolar, Rats, Sprague-Dawley, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Microscopy, Electron, Transmission, Rats, Osteopontin, Matrix Metalloproteinase 10, Nanoparticles, Transforming Growth Factor beta1

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