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Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver
Author(s) -
Carrola Joana,
Bastos Verónica,
DanieldaSilva Ana L.,
Gil Ana M.,
Santos Conceição,
Oliveira Helena,
Duarte Iola F.
Publication year - 2020
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.202000095
Subject(s) - chemistry , metabolomics , reactive oxygen species , silver nanoparticle , glycolysis , glutathione , metabolic pathway , biochemistry , intracellular , macrophage , biophysics , metabolism , enzyme , nanoparticle , nanotechnology , biology , chromatography , in vitro , materials science
This study employed NMR metabolomics to characterize macrophage responses to subtoxic concentrations of silver nanoparticles (AgNPs ca. 30 nm) and ionic silver (Ag + ), with a view to further elucidate their immunomodulatory activity at the cell metabolism level. Exposure to AgNPs caused RAW 264.7 macrophages to decrease intracellular glucose utilization, possibly due to interference with glycolytic enzymes, and to reprogram the TCA cycle towards anaplerotic fueling and production of anti‐inflammatory metabolites (e.g. itaconate and creatine). Moreover, AgNPs‐exposed cells were able to control the levels of reactive oxygen/nitrogen species (ROS/RNS), likely through upregulation of glutathione synthesis. On the other hand, macrophages exposed to Ag + at equivalent subtoxic concentrations showed reduced metabolic activity, lower ability to counterbalance ROS/RNS and alterations in membrane‐related lipids. Overall, the metabolomics approach hereby employed provided novel insights into the differential effects of AgNPs and Ag + , which help explain the lower toxic potential of nanosilver than silver ions.