CNR ExploRA

Articolo in rivista, 2021, ENG, 10.1016/j.impact.2021.100313

Pulmonary toxicity and gene expression changes after short-term inhalation exposure to surface-modified copper oxide nanoparticles

Gosens I.; Costa P.M.; Olsson M.; Stone V.; Costa A.L.; Brunelli A.; Badetti E.; Bonetto A.; Bokkers B.G.H.; de Jong W.H.; Williams A.; Halappanavar S.; Fadeel B.; Cassee F.R.

National Institute for Public Health and the Environment, Bilthoven, National Institute for Public Health and the Environment, Bilthoven, The Netherlands;, , Netherlands; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;, , Sweden; UCIBIO - Applied molecular Biosciences Unit, Department of Life Sciences, School of Science and Technology, NOVA University of Lisbon, Caparica, UCIBIO - Applied molecular Biosciences Unit, Department of Life Sciences, School of Science and Technology, NOVA University of Lisbon, Caparica, Portugal;, , Portugal; Heriot-Watt University, School of Life Sciences, Edinburgh, Heriot-Watt University, School of Life Sciences, Edinburgh, UK;, , United Kingdom; National Research Council, Institute of Science and Technology for Ceramics, Faenza, National Research Council, Institute of Science and Technology for Ceramics, Faenza, Italy;, , , Italy; National Research Council, Institute of Science and Technology for Ceramics, Faenza, National Research Council, Institute of Science and Technology for Ceramics, Faenza, Italy;, , , Italy; Department of Environmental Sciences, Informatics and Statistics, University of Venice Ca' Foscari, Venice, Department of Environmental Sciences, Informatics and Statistics, University of Venice Ca' Foscari, Venice, Italy;, , Italy; Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, ON, Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario, Canada;, , Canada; Department of Biology, University of Ottawa, Ottawa, ON, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada, , Canada; Institute for Risk Assessment Studies, Utrecht University, Utrecht, Institute for Risk Assessment Studies, Utrecht University, Utrecht, The Netherlands., , , Netherlands; Institute for Risk Assessment Studies, Utrecht University, Utrecht, Institute for Risk Assessment Studies, Utrecht University, Utrecht, The Netherlands., , , Netherlands

Copper oxide nanoparticles (CuO NPs) have previously been shown to cause dose-dependent pulmonary toxicity following inhalation. Here, CuO NPs (10 nm), coated with polyethylenimine (PEI) or ascorbate (ASC) resulting in positively or negatively charged NPs, respectively, were evaluated. Rats were exposed nose-only to similar exposure dose levels of ASC or PEI coated CuO NPs for 5 consecutive days. On day 6 and day 27 post-exposure, pulmonary toxicity markers in bronchoalveolar lavage fluid (BALF), lung histopathology and genome-wide transcriptomic changes in lungs, were assessed. BALF analyses showed a dose-dependent pulmonary inflammation and cell damage, which was supported by the lung histopathological findings of hypertrophy/hyperplasia of bronchiolar and alveolar epithelium, interstitial and alveolar inflammation, and paracortical histiocytosis in mediastinal lymph nodes for both types of CuO NPs. Transcriptomics analysis showed that pathways related to inflammation and cell proliferation were significantly activated. Additionally, we found evidence for the dysregulation of drug metabolism-related genes, especially in rats exposed to ASC-coated CuO NPs. Overall, no differences in the type of toxic effects and potency between the two surface coatings could be established, except with respect to the (regional) dose that initiates bronchiolar and alveolar hypertrophy. This disproves our hypothesis that differences in surface coatings affect the pulmonary toxicity of CuO NPs.

NanoImpact (Amsterdam) Online 22 , pp. 1–13