Browse > Article
http://dx.doi.org/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  

Rice, Kevin M. (Center for Diagnostic Nanosystems, Marshall University)
Nalabotu, Siva K. (Center for Diagnostic Nanosystems, Marshall University)
Manne, Nandini D.P.K. (Center for Diagnostic Nanosystems, Marshall University)
Kolli, Madhukar B. (Center for Diagnostic Nanosystems, Marshall University)
Nandyala, Geeta (Center for Diagnostic Nanosystems, Marshall University)
Arvapalli, Ravikumar (Center for Diagnostic Nanosystems, Marshall University)
Ma, Jane Y. (Health Effects Laboratory Division, NIOSH)
Blough, Eric R. (Center for Diagnostic Nanosystems, Marshall University)
Publication Information
Journal of Preventive Medicine and Public Health / v.48, no.3, 2015 , pp. 132-141 More about this Journal
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 ($CeO_2$) 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 $CeO_2$ 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 $CeO_2$ instillation (p<0.05). Conclusions: Taken together, these data suggest that high-dose respiratory exposure to $CeO_2$ 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.
Keywords
Cerium oxide nanoparticles; Lung; Inflammation; Mitogen-activated protein kinases;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Heckert EG, Seal S, Self WT. Fenton-like reaction catalyzed by the rare earth inner transition metal cerium. Environ Sci Technol 2008;42(13):5014-5019.   DOI
2 Bumajdad A, Eastoe J, Mathew A. Cerium oxide nanoparticles prepared in self-assembled systems. Adv Colloid Interface Sci 2009;147-148:56-66.   DOI
3 Park B, Martin P, Harris C, Guest R, Whittingham A, Jenkinson P, et al. Initial in vitro screening approach to investigate the potential health and environmental hazards of Enviroxtrade mark - a nanoparticulate cerium oxide diesel fuel additive. Part Fibre Toxicol 2007;4:12.   DOI
4 Karakoti AS, Monteiro-Riviere NA, Aggarwal R, Davis JP, Narayan RJ, Self WT, et al. Nanoceria as antioxidant: synthesis and biomedical applications. JOM (1989) 2008;60(3):33-37.   DOI
5 Niu J, Azfer A, Rogers LM, Wang X, Kolattukudy PE. Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. Cardiovasc Res 2007;73(3): 549-559.   DOI
6 Das M, Patil S, Bhargava N, Kang JF, Riedel LM, Seal S, et al. Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 2007;28(10):1918-1925.   DOI
7 Colon J, Herrera L, Smith J, Patil S, Komanski C, Kupelian P, et al. Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. Nanomedicine 2009;5(2):225-231.   DOI
8 Lin W, Huang YW, Zhou XD, Ma Y. Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol 2006;25(6):451-457.   DOI
9 Eom HJ, Choi J. Oxidative stress of $CeO_{2}$ nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B. Toxicol Lett 2009;187(2):77-83.   DOI
10 He X, Zhang H, Ma Y, Bai W, Zhang Z, Lu K, et al. Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation.Nanotechnology 2010;21(28):285103.   DOI
11 Cassee FR, van Balen EC, Singh C, Green D, Muijser H, Weinstein J, et al. Exposure, health and ecological effects review of engineered nanoscale cerium and cerium oxide associated with its use as a fuel additive. Crit Rev Toxicol 2011;41(3):213-229.   DOI
12 Samet JM, Graves LM, Quay J, Dailey LA, Devlin RB, Ghio AJ, et al. Activation of MAPKs in human bronchial epithelial cells exposed to metals. Am J Physiol 1998;275(3 Pt 1):L551-L558.
13 Ma JY, Zhao H, Mercer RR, Barger M, Rao M, Meighan T, et al. Cerium oxide nanoparticle-induced pulmonary inflammation and alveolar macrophage functional change in rats. Nanotoxicology 2011;5(3):312-325.   DOI
14 Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem 1996;271(8):4138-4142.   DOI
15 Tournier C, Thomas G, Pierre J, Jacquemin C, Pierre M, Saunier B. Mediation by arachidonic acid metabolites of the H2O2-induced stimulation of mitogen-activated protein kinases (extracellular-signal-regulated kinase and c-Jun NH2-terminal kinase). Eur J Biochem 1997;244(2):587-595.   DOI
16 Nalabotu SK, Kolli MB, Triest WE, Ma JY, Manne ND, Katta A, et al. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats. Int J Nanomedicine 2011;6:2327-2335.
17 Ma JY, Zhao H, Mercer RR, Barger M, Rao M, Meighan T, et al. Cerium oxide nanoparticle-induced pulmonary inflammation and alveolar macrophage functional change in rats. Nanotoxicology 2011;5(3):312-325.   DOI
18 Wu M, Liu H, Fannin J, Katta A, Wang Y, Arvapalli RK, et al. Acetaminophen improves protein translational signaling in aged skeletal muscle. Rejuvenation Res 2010;13(5):571-579.   DOI
19 Kakarla SK, Fannin JC, Keshavarzian S, Katta A, Paturi S, Nalabotu SK, et al. Chronic acetaminophen attenuates age-associated increases in cardiac ROS and apoptosis in the Fischer Brown Norway rat. Basic Res Cardiol 2010;105(4):535-544.   DOI
20 Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci 2004;117(Pt 8):1281-1283.   DOI
21 Park EJ, Choi J, Park YK, Park K. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. Toxicology 2008;245(1-2):90-100.   DOI
22 Donaldson K, Aitken R, Tran L, Stone V, Duffin R, Forrest G, et al. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 2006; 92(1):5-22.   DOI
23 Park EJ, Yoon J, Choi K, Yi J, Park K. Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology 2009;260(1-3):37-46.   DOI
24 Ren H, Huang X. Polyacrylate nanoparticles: toxicity or new nanomedicine? Eur Respir J 2010;36(1):218-221.   DOI
25 Bergamaschi E, Bussolati O, Magrini A, Bottini M, Migliore L, Bellucci S, et al. Nanomaterials and lung toxicity: interactions with airways cells and relevance for occupational health risk assessment. Int J Immunopathol Pharmacol 2006;19(4 Suppl):3-10.
26 Stone V, Johnston H, Clift MJ. Air pollution, ultrafine and nanoparticle toxicology: cellular and molecular interactions. IEEE Trans Nanobioscience 2007;6(4):331-340.   DOI
27 Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Moller P. Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 2009;117(5):703-708.   DOI
28 Jeong YS, Oh WK, Kim S, Jang J. Cellular uptake, cytotoxicity, and ROS generation with silica/conducting polymer core/shell nanospheres. Biomaterials 2011;32(29):7217-7225.   DOI
29 Li N, Xia T, Nel AE. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 2008;44(9):1689-1699.   DOI
30 Koike E, Kobayashi T. Chemical and biological oxidative effects of carbon black nanoparticles. Chemosphere 2006;65(6): 946-951.   DOI
31 Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2007;2(4):MR17-MR71.   DOI
32 Marano F, Hussain S, Rodrigues-Lima F, Baeza-Squiban A, Boland S. Nanoparticles: molecular targets and cell signalling. Arch Toxicol 2011;85(7):733-741.   DOI
33 Lenaz G. The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 2001;52(3-5):159-164.   DOI
34 Kuwano K. Epithelial cell apoptosis and lung remodeling. Cell Mol Immunol 2007;4(6):419-429.
35 Kang KA, Wang ZH, Zhang R, Piao MJ, Kim KC, Kang SS, et al. Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways. Int J Mol Sci 2010;11(11):4348-4360.   DOI
36 Blank VC, Pena C, Roguin LP. STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-alpha2b peptide. Exp Cell Res 2010;316(4):603-614.   DOI