From the Cover: Metabolism Modulation in Different Organs by Silver Nanoparticles: An NMR Metabolomics Study of a Mouse Model

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.

keywords

OXIDATIVE STRESS; WISTAR RATS; TOXICITY; METABONOMICS; CELLS; GENOTOXICITY; ABSORPTION; BIOMARKERS; EXCRETION; DRESSINGS

subject category

Toxicology

authors

Jarak, I; Carrola, J; Barros, AS; Gil, AM; Pereira, MD; Corvo, ML; Duarte, IF

Groups

G4 - Renewable Materials and Circular Economy
G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2013)

Metabolic profiling: a novel tool for evaluation of the toxicological and biological effects of nanomaterials (PTDC/SAU-TOX/120953/2010)

acknowledgements

This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (UID/CTM/50011/2013) and iMed.ULisboa (UID/DTP/04138/2013) financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. Funding to the project FCOMP-01-0124-FEDER-021456 (PTDC/SAU-TOX/120953/2010) by FEDER through COMPETE and by national funds through FCT is acknowledged. J.C. and I.F.D. acknowledge FCT/MCTES for the grant (SFRH/BD/79494/2011) and the "IF2014" research contract, respectively.