authors |
Jarak, I; Carrola, J; Barros, AS; Gil, AM; Pereira, MD; Corvo, ML; Duarte, IF |
nationality |
International |
journal |
TOXICOLOGICAL SCIENCES |
author keywords |
silver nanoparticles (AgNPs); NMR metabolomics; BALB; c mice; invivo; metabolism; nanotoxicity |
keywords |
OXIDATIVE STRESS; WISTAR RATS; TOXICITY; METABONOMICS; CELLS; GENOTOXICITY; ABSORPTION; BIOMARKERS; EXCRETION; DRESSINGS |
abstract |
Although silver nanoparticles (AgNPs) are widely disseminated and show great potential in the biomedical field, there is a recognized need to better understand their action at the metabolic and functional levels. In this work, we have used NMR metabolomics, together with conventional clinical chemistry and histological examination, to characterize multi-organ and systemic metabolic responses to AgNPs intravenously administered to mice at 8 mg/kg body weight (a dose not eliciting overt toxicity). The major target organs of AgNPs accumulation, liver and spleen, showed the greatest metabolic changes, in a clear 2-stage response. In particular, the liver of dosed mice was found to switch from glycogenolysis and lipid storage, at 6 h postinjection, to glycogenesis and lipolysis, at subsequent times up to 48 h. Moreover, metabolites related to antioxidative defense, immunoregulation and detoxification seemed to play a crucial role in avoiding major hepatic damage. The spleen showed several early changes, including depletion of several amino acids, possibly reflecting impairment of hemoglobin recycling, while only a few differences remained at 48 h postinjection. In the heart, the metabolic shift towards TCA cycle intensification and increased ATP production possibly reflected a beneficial adaptation to the presence of AgNPs. On the other hand, the TCA cycle appeared to be down regulated in the lungs of injected mice, which showed signs of inflammation. Thekidneys showed the mildest metabolic response to AgNPs. Overall, this study has shown that NMR metabolomics is a powerful tool to monitor invivo metabolic responses to nanoparticles, revealing unforeseen effects. |
publisher |
OXFORD UNIV PRESS |
issn |
1096-6080 |
isbn |
1096-0929 |
year published |
2017 |
volume |
159 |
issue |
2 |
beginning page |
422 |
ending page |
435 |
digital object identifier (doi) |
10.1093/toxsci/kfx142 |
web of science category |
Toxicology |
subject category |
Toxicology |
unique article identifier |
WOS:000412203900012
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ciceco authors
impact metrics
journal analysis (jcr 2019):
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journal impact factor |
3.703 |
5 year journal impact factor |
4.135 |
category normalized journal impact factor percentile |
82.065 |
dimensions (citation analysis):
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altmetrics (social interaction):
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