Induction of pulmonary fibrosis by cerium oxide nanoparticles
Open accessAbstract
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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Ma et al. reported prominent signs of fibrosis after single intratracheal instillation.
“Ma et al. [45] reported prominent signs of fibrosis after single intratracheal instillation.”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [45]
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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)
- PMC
- PMC4697452
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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