Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles
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 flu...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Jung-Taek Kwon Yoonjin Kim Seonyoung Choi Byung-ll Yoon Hyun-Sook Kim Ilseob Shim Donggeun Sul |
| author_facet | Jung-Taek Kwon Yoonjin Kim Seonyoung Choi Byung-ll Yoon Hyun-Sook Kim Ilseob Shim Donggeun Sul |
| author_sort | Jung-Taek Kwon |
| collection | DOAJ |
| description | 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-α, 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 α1 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. |
| first_indexed | 2024-03-09T19:00:34Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:34Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-62a6acc232b5436e87b00ec79b25710d2023-11-24T05:05:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211326510.3390/ijms232113265Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide NanoparticlesJung-Taek Kwon0Yoonjin Kim1Seonyoung Choi2Byung-ll Yoon3Hyun-Sook Kim4Ilseob Shim5Donggeun Sul6Environmental Health Research Department, National Institute of Environmental Research, Incheon 22689, KoreaEnvironmental Health Research Department, National Institute of Environmental Research, Incheon 22689, KoreaGraduate School of Medicine, Korea University, 73 Inchon-ro, Sungbuk-ku, Seoul 136-705, KoreaCollege of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, KoreaDepartment of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju 28503, KoreaEnvironmental Health Research Department, National Institute of Environmental Research, Incheon 22689, KoreaGraduate School of Medicine, Korea University, 73 Inchon-ro, Sungbuk-ku, Seoul 136-705, KoreaCopper 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-α, 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 α1 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.https://www.mdpi.com/1422-0067/23/21/13265bronchoalveolar lavage fluidcopper oxidenanoparticlesproteomicsrat lung |
| spellingShingle | Jung-Taek Kwon Yoonjin Kim Seonyoung Choi Byung-ll Yoon Hyun-Sook Kim Ilseob Shim Donggeun Sul Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles International Journal of Molecular Sciences bronchoalveolar lavage fluid copper oxide nanoparticles proteomics rat lung |
| title | Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles |
| title_full | Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles |
| title_fullStr | Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles |
| title_full_unstemmed | Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles |
| title_short | Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles |
| title_sort | pulmonary toxicity and proteomic analysis in bronchoalveolar lavage fluids and lungs of rats exposed to copper oxide nanoparticles |
| topic | bronchoalveolar lavage fluid copper oxide nanoparticles proteomics rat lung |
| url | https://www.mdpi.com/1422-0067/23/21/13265 |
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