Transcriptomic Implications of Toxic Effects of Nanoparticles on Metabolic Pathways of Liver Cells

Abstract

AbstractWhile nanoparticles find applications in various fields such as cosmetics, drug delivery, and medicine, they also exhibit significant drawbacks. The adverse effects remain inadequately comprehended and necessitate further analysis. This study focuses on assessing the impacts of diverse nanoparticles on HepaRG cell spheroids prior to conducting RNA-Seq analysis, cell viability assays were performed to determine the concentrations of NPs that induce toxicity while maintaining 80% cell viability—a concentration sufficient to cause toxicity without total cell death. To mimic the cellular microenvironment, HepaRG cell spheroids were generated and treated with four distinct nanoparticles of varying sizes. Subsequently, these spheroids underwent RNA-seq analysis to identify specific genes responsive to nanoparticle-induced toxicity. Our findings demonstrate that exposure to nanoparticles substantially modifies gene transcription. Notably, 38 differentially expressed genes were shared across all four types of nanoparticles. These genes were linked to distinct categories of Gene Ontology (GO) terms, thereby clarifying their functions and metabolic pathways through GO and KEGG pathway analyses. Remarkably, processes such as apoptosis, sensitivity to metal ions, hypoxia, and oxidative stress consistently exhibited significant enrichment across all nanoparticle types.Abstract Figure