Paper Title

Abstract - Silver nanoparticles (AgNPs) have excellent physicochemical properties and are widely used in various antibacterial products. There are many opportunities for human body exposure. Ferroptosis is a newly discovered, iron-mediated cell death that is involved in the development and progression of some neurological diseases. The purpose of this study is to explore ferroptosis induced by AgNPs on mouse hippocampal neuron cell line (HT22) and its mechanism. Cell viability was determined by CCK-8 analysis. Total glutathione (GSH) was measured by a commercial GSH kit. Malondialdehyde (MDA) level was measured by a commercial MDA kit. The protein expression levels related ferroptosis was measured by Western blotting assay. The results showed that (1) AgNPs-induced cell death involved ferroptosis. Ferroptosis inhibitors desferrioxamine (DFO) and ferrostatin-1 (Fer-1) could significantly inhibit the cytotoxicity caused by AgNPs; (2) AgNPs could cause iron homeostasis disorder in HT22 cells by affecting the expression levels of ferritin heteropolymers ferritin light chain (FTL), ferritin heavy chain (FTH1) and iron importers transferrin receptor protein 1 (TFRC); (3) AgNPs-triggered ferroptosis was related to the increase of lipid peroxide MDA, the depletion of reduced glutathione (GSH), the down-regulation of glutathione peroxidase 4 (GPx4) and the up-regulation of the system Xc- transporter subunit cystine/glutamate transporter (SLC7A11). Our data provided a new mechanism basis for ferroptosis as a new cell death phenotype induced by AgNPs. The deeper mechanism and its relationship with the neurotoxicity of AgNPs need to be further studied. Keywords - Nanotoxicity; Silver Nanoparticles; Ferroptosis; Lipid Peroxidation