resumo
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.
palavras-chave
TOXICITY MECHANISM; SUCCINATE-DEHYDROGENASE; CELLS STRUCTURE; IN-VITRO; ITACONATE; HEXOKINASE; SIZE
categoria
Chemistry
autores
Carrola, J; Bastos, V; Daniel-da-Silva, AL; Gil, AM; Santos, C; Oliveira, H; Duarte, IF
nossos autores
Ana Luísa Daniel da Silva
Investigador Principal
Ana Maria Pissarra Coelho Gil
Professor Associado com Agregação
Helena Oliveira
Bolseiro de pós-Doutoramento
Iola Melissa Fernandes Duarte
Investigador Principalagradecimentos
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020 & UIDP/50011/2020), and CESAM (UIDB/50017/2020 & UIDP/50017/2020), financed by national funds through the Foundation for Science and Technology/MCTES. Funding to the project FCOMP-01-0124-FEDER-021456 (PTDC/SAU-TOX/120953/2010) by FEDER through COMPETE and by national funds through FCT, financial support from the European Union Framework Programme for Research and Innovation HORIZON 2020, under the TEAMING Grant agreement No 739572 - The Discoveries CTR, and the FCT-awarded research grants or contracts (SFRH/BD/79494/2011, IF/01439/2014, IF/00405/2014, CEECIND/04050/2017, CDL-CTTRI-161-ARH/2018) are also acknowledged. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).