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 8mg/kg body weight (a dose not eliciting overt toxicity). Themajor target organs of AgNPs accumulation, liver and spleen, showed the greatestmetabolic changes, in a clear 2-stage response. In particular, the liver of dosed mice was found to switch fromglycogenolysis and lipid storage, at 6h 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 48h 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. The kidneys showed the mildestmetabolic response to AgNPs. Overall, this study has shown that NMRmetabolomics is a powerful tool to monitor in vivo metabolic responses to nanoparticles, revealing unforeseen effects.