Biochemical response of human endothelial and fibroblast cells to silver nanoparticles

Nowadays the bactericidal and antimicrobial properties of silver nanoparticles, AgNPs, in addition to their cytotoxic effects, have been explored to properly modulate cell biochemistry processes in order to improve the healing of wounds. Herein we investigate the cytotoxicity and metabolic profiling of two human cell lineages, the fibroblast FN1 and endothelial HUV-EC-C, planning doses of AgNPs and incubation times. Cytotoxicity assays showed consistent decrease in proliferation rates, viable cells number, and average surface areas. Metabolomics based on proton Nuclear Magnetic Resonance was successfully used to obtain quantitative and qualitative changes in metabolic events triggered by silver treatments. The metabolic profiling provided by endo- and exometabolome revealed biochemical changes induced on treated cells compared to controls. Glycolytic pathway is up-regulated due to the elevation in glucose consumption; however, the consequent elevation in pyruvate production seems to be wasted by cells to generate energy by aerobic means that are choosing to oxidize it to acetate. Aminoacid metabolism is down-regulated, signalizing the protein degradation mechanism. Tricarboxylic Acid Cycle is also down-regulated, indicating a starvation situation once succinate was left over in the culture media. Concurrently, the ketogenic pathway is up-regulated due to the excess of acetone. Changes in pyroglutamate metabolism were detected indicating the up-regulation of glutathione biosynthesis used to equilibrate the effects induced by oxidative stress, in accordance with the N-Acetylcysteine finds. Phospholipid metabolism is down-regulated, as revealed by the changes in O-Phosphocholine and Sn-Glycerol-3-PC levels, signaling reduction in the cellular proliferation rates. To the best of our knowledge, this is the first report describing AgNP-induced changes in the UDP-GlcNAc levels, which plays an essential role in modifying nucleocytoplasmic proteins. In summary, AgNPs can induce oxidative stress and cytotoxicity in endothelial and fibroblast cells, influencing their endo- and exometabolome.