Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs

Rice, Kevin M; Nalabotu, Siva K; Manne, Nandini D P K; Kolli, Madhukar B; Nandyala, Geeta; Arvapalli, Ravikumar; Ma, Jane Y; Blough, Eric R

J Prev Med Public Health. 2015 May;48(3):132-141. 10.3961/jpmph.15.006.

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs

Affiliations

¹Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA. rice9@marshall.edu
²School of Kinesiology, College of Health Professions, Marshall University, Huntington, WV, USA.
³Biotechnology Department, West Virginia State University, Institute, WV, USA.
⁴Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
⁵Department of Pharmacology, Physiology and Toxicology, Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, USA.
⁶Health Effects Laboratory Division, NIOSH, Morgantown, WV, USA.
⁷Department of Pharmaceutical Sciences, Marshall University School of Pharmacy, Huntington, WV, USA.

KMID: 2381462
DOI: http://doi.org/10.3961/jpmph.15.006

Abstract

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.

Keyword

Cerium oxide nanoparticles; Lung; Inflammation; Mitogen-activated protein kinases

MeSH Terms

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs

Abstract

Keyword

MeSH Terms

Cited

Save citations to file

Email citations