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

• Published in: Journal of preventive medicine and public health Vol. 48; no. 3; pp. 132 - 141
• Main Authors: Rice, Kevin M, Nalabotu, Siva K, Manne, Nandini D P K, Kolli, Madhukar B, Nandyala, Geeta, Arvapalli, Ravikumar, Ma, Jane Y, Blough, Eric R
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Preventive Medicine 01.05.2015; 대한예방의학회
• Subjects: Animals; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Caspase 3 - metabolism; Cerium - chemistry; Cerium oxide nanoparticles; Inflammation; Lung; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Metal Nanoparticles - chemistry; Metal Nanoparticles - toxicity; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-activated protein kinases; Mitogen-Activated Protein Kinases - metabolism; Original; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; 예방의학; Inflammation; Cerium oxide nanoparticles; Lung; Mitogen-activated protein kinases
• ISSN: 1975-8375; 2233-4521
• DOI: 10.3961/jpmph.15.006

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. 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. 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). 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.