Silica-cSilica-coated-magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate discovered using integrated omics analysisoated-magnetic-nanoparticle-induced cytotoxicity is reduced in microglia by glutathione and citrate discovered using integrated omics analysis

ABSTRACT: Exposure to nanoparticles leads to their accumulation in the brain, but drug development to counteract this nanotoxicity remains challenging. Here we assessed the effect of silica-coated-magnetic nanoparticles containing the rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)] on microglia through integration of transcriptomics, proteomics, and metabolomics. Intracellular reactive oxygen species production, an inflammatory response, and morphological activation of cells were greater, but glucose uptake was lower in MNPs@SiO2(RITC)-treated BV2 microglia and primary rat microglia. Expression of 121 genes, and levels of 45 proteins and 17 metabolites related to the above phenomena changed in MNPs@SiO2(RITC)-treated microglia. We integrated the three omics datasets and generated a single network using a machine learning algorithm. We screened 19 compounds and predicted their effects on nanotoxicity within the triple-omics network. A combination of glutathione and citrate attenuated nanotoxicity induced by MNPs@SiO2(RITC) and ten other nanoparticles in vitro and in the murine brain, protecting mostly the hippocampus and thalamus.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Microglial Cell

DISEASE(S): Toxic Encephalopathy

SUBMITTER: Ju Yeon Lee  

LAB HEAD: Gwang Lee

PROVIDER: PXD020225 | Pride | 2022-02-15

REPOSITORIES: Pride