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
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
António de Sousa Barros
Post-doc Fellowship
Iola Melissa Fernandes Duarte
Principal Researcher
Ivana Jarak
Post-doc Fellowship
Joana Carolina Quintela Carrola
PhD Student
Maria de Lourdes Gomes Pereira
Associate Professor with Aggregation
Maria João Portela e Sá Pereira
Post-Doc Fellowshipacknowledgements
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.