Abstract
The respiratory tract is the route of entry for accidentally inhaled AgNPs, which can reach the lungs and redistribute to other main organs through systemic circulation. In the present work, we aimed to evaluate silver biodistribution and biological effects after 1 or 2 intratracheal instillations (IT) of two differently sized PVP-coated AgNPs (5 and 50 nm–3 mg/kg) and ionic silver (AgNO3–1 mg/kg bw) in mice. Furthermore, nuclear magnetic resonance (NMR) metabolomics was applied to unveil pulmonary metabolic variations. Animals exposed to 5 nm AgNP (AgNP5) showed higher levels of ionic silver in organs, especially in the lung, spleen, kidney and liver, while animals exposed to 50 nm AgNP (AgNP50) showed higher levels of silver in the blood. Animals exposed to AgNP50 excreted higher amounts of silver than those exposed to AgNP5, which is consistent with higher tissue accumulation of silver in animals exposed to the latter. Lung metabolic profiling revealed several Ag-induced alterations in metabolites involved in different pathways, such as glycolysis and tricarboxylic acid (TCA) cycle, amino acid and phospholipid metabolism, and antioxidant defense. Notably, most of the metabolic changes observed after 1 IT were absent in animals subjected to 2 IT of AgNO3, or reversed for AgNPs, suggesting adaptation mechanisms to cope with the initial insult and recover homeostasis.
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Acknowledgements
The authors would like to thank the colleagues Sofie Van Den Broucke and Hanne Vriens for their help and support in carrying out some of this work. I.F.D and H.O acknowledge FCT/MCTES for research contracts, respectively, under the Programs “FCT Researcher” (IF/01439/2014), and “Stimulus to Scientific Employment” (CEECIND/04050/2017).
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This work was supported by CESAM [FCT Ref. UIDP/50017/2020+UIDB/50017/2020] and CICECO-Aveiro Institute of Materials [FCT Ref. UIDB/50011/2020 & UIDP/50011/2020], financed by the national funds through the Foundation for Science and Technology/MCTES. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). Funding to the project PTDC/AAC-AMB/113649 by FEDER through COMPETE and by national funds through FCT, financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No 739572 - The Discoveries CTR, and the FCT-awarded grant [SFRH/BD/91270/2012 to F.R] are acknowledged.
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FR, IFD, CS, PHMH, and HO designed the study. FR, IFD, and RJBP performed the experiments. FR, RJBP, IFD, and H.O prepared the original draft. CS, PHMH, and HO were responsible for the oversight of the project. All authors critically read and approved the final manuscript.
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All experimental procedures were approved (N° 054/2015) by the Ethical Committee for Animal Experiments of the KU Leuven (https://admin.kuleuven.be/raden/en/animal-ethics-committee) in compliance with institutional, national, and international guidelines. The functioning of the Ethical Committee for Animal Experiments of the KU Leuven is monitored by the competent authorities. In this context, the authorities can participate in all meetings and consult all related documents.
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Rosário, F., Duarte, I.F., Pinto, R.J. et al. Biodistribution and pulmonary metabolic effects of silver nanoparticles in mice following acute intratracheal instillations. Environ Sci Pollut Res 28, 2301–2314 (2021). https://doi.org/10.1007/s11356-020-10563-z
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DOI: https://doi.org/10.1007/s11356-020-10563-z