Biodistribution and pulmonary metabolic effects of silver nanoparticles in mice following acute intratracheal instillati
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RESEARCH ARTICLE
Biodistribution and pulmonary metabolic effects of silver nanoparticles in mice following acute intratracheal instillations Fernanda Rosário 1 & Iola F. Duarte 2 & Ricardo J.B. Pinto 2 & Conceição Santos 3 & Peter H.M. Hoet 4 & Helena Oliveira 1 Received: 16 January 2020 / Accepted: 18 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Silver nanoparticles . In vivo . Intratracheal instillation . Biodistribution . Excretion . NMR metabolomics
Introduction Silver nanoparticles (AgNPs) have been extensively produced and incorporated into consumer products, such as food Responsible editor: Mohamed M. Abdel-Daim Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11356-020-10563-z) contains supplementary material, which is available to authorized users. * Iola F. Duarte [email protected] * Helena Oliveira [email protected] 1
Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal
2
CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-093 Aveiro, Portugal
3
Department of Biology, LAQV/REQUIMTE, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
4
Occupational and Environmental Toxicology, KU Leuven, ON1 Campus Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
packaging material, food supplements, textiles, and spray products, mainly due to their antimicrobial properties. Moreover, emergent evidence on AgNPs’ potent anti-inflammatory, antiviral, and/or anticancer activities (Wei et al. 2015; Lee and Jun 2019; Paladini and Pollini 2019) makes it likely that the biomedical app
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