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Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticlesopen access

Authors
Kwon, Jung-TaekKim, YoonjinChoi, SeonyoungYoon, Byung-IlKim, Hyun-SookShim, IlseobSul, Donggeun
Issue Date
Nov-2022
Publisher
MDPI
Keywords
bronchoalveolar lavage fluid; copper oxide; nanoparticles; proteomics; rat lung
Citation
International Journal of Molecular Sciences, v.23, no.21
Indexed
SCIE
SCOPUS
Journal Title
International Journal of Molecular Sciences
Volume
23
Number
21
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/61862
DOI
10.3390/ijms232113265
ISSN
1661-6596
1422-0067
Abstract
Copper oxide nanoparticles (CuO NPs) were intratracheally instilled into lungs at concentrations of 0, 0.15, and 1.5 mg/kg bodyweight to 7-week-old Sprague-Dawley rats. The cytotoxicity, immunotoxicity, and oxidative stress were evaluated, followed by proteomic analysis of bronchoalveolar lavage fluid (BALF) and lungs of rats. The CuO NPs-exposed groups revealed dose-dependent increases in total cells, polymorphonuclear leukocytes, lactate dyhydrogenase, and total protein levels in BALF. Inflammatory cytokines, including macrophage inflammatory protein-2 and tumor necrosis factor-alpha, were increased in the CuO NPs-treated groups. The expression levels of catalase, glutathione peroxidase-1, and peroxiredoxin-2 were downregulated, whereas that of superoxide dismutase-2 was upregulated in the CuO NPs-exposed groups. Five heat shock proteins were downregulated in rats exposed to high concentrations of CuO NPs. In proteomic analysis, 17 proteins were upregulated or downregulated, and 6 proteins were validated via Western blot analysis. Significant upregulation of 3-hydroxy-3-methylglutaryl-CoA synthase and fidgetin-like 1 and downregulation of annexin II, HSP 47 and proteasome alpha 1 occurred in the CuO NPs exposed groups. Taken together, this study provides additional insight into pulmonary cytotoxicity and immunotoxicity as well as oxidative stress in rats exposed to CuO NPs. Proteomic analysis revealed potential toxicological biomarkers of CuO NPs, which also reveals the toxicity mechanisms of CuO NPs.
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