Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs
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OBJECTIVES: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. METHODS: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. RESULTS: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05). CONCLUSIONS: Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.
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Elevated cleaved caspase-3 levels have been reported after CeO2 nanoparticle instillation.
“Elevated cleaved caspase-3 levels have been reported after CeO2 nanoparticle instillation [30].”
From Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats (2017) · cites this paper as [30]
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- Authors
- Rice, K. M., Nalabotu, S. K., Manne, N. D. P. K., Kolli, M. B., Nandyala, G., Arvapalli, R., Ma, J. Y., & Blough, E. R.
- Affiliations
- West Virginia State University (US)
- Marshall University (US)
- National Institute for Occupational Safety and Health (US)
- Corresponding author
- Rice, Kevin M.
- Venue
- Journal of Preventive Medicine and Public Health
- Published
- 2015-05-18
- Volume
- 48
- Issue
- 3
- Pages
- 132-141
- ISSN
- 1975-8375 (ISSN-L)
- 2233-4521
- PMC
- PMC4484279
- OpenAlex
- W2261338968
- Cited by
- 29
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 1
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Preventive Medicine and Public Health (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- cerium oxide nanoparticles, lung inflammation, apoptosis, mitogen-activated protein kinase, p38 MAPK, ERK1/2, Bax/Bcl-2 ratio, cleaved caspase-3, lung histopathology, nanoparticle toxicity
- MeSH terms
- Animals, Cerium, Inflammation, Lung, Male, Phosphorylation, Signal Transduction, Rats, Sprague-Dawley, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, bcl-2-Associated X Protein, Rats, Caspase 3, Metal Nanoparticles
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