Ferroptosis inhibitor alleviates cytotoxicity induced by cobalt nanoparticles through reactive oxygen species attenuation

Abstract

Background Currently, tissue damage induced by cobalt nanoparticles (CoNPs) are the most noticeable adverse effect in the patients with metal-on-metal (MOM) hip prostheses. Therefore, effective therapeutic strategy is needed to limit the toxicity of CoNPs. In this study, we aimed to investigate the protective effect of ferroptosis inhibitor on CoNPs-induced cytotoxicity. Methods To evaluate the detoxification effect of ferroptosis inhibitor, MG-63 cells were treated with CoNPs and ferroptosis inhibitor for 24 h. The cell viabilities were measured by CCK-8 assay. The expressions of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) were examined by western blot. Reactive oxygen species (ROS) and the GSH level were measured by the relevant kits. The cell apoptosis was detected by flow cytometry. The serum levels of inflammatory cytokines were measured with Elisa.Results The cytotoxic effects of CoNPs were time- and dose-dependent. In addition, CoNPs elicited a significant (p <0.05) reduction in cell viability and the glutathione (GSH) level with a concomitant increase in ROS generation and inflammatory cytokines such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) after 24 hours of exposure. Deferiprone (DFP) provided significant protection for cells after treatment with CoNPs. Western blot analysis demonstrated that CoNPs decreased the expression of GPX4 and SLC7A11, and treatment with DFP inhibited the decrease.Conclusions CoNPs were highly cytotoxic and ferroptosis inhibitor DFP has a detoxification effect on cytotoxicity induced by CoNPs. Ferroptosis plays an important role in the process that CoNPs induced the cytotoxicity. The effectiveness of ferroptosis inhibition on MG-63 cells may initiate the development of novel strategies for reducing the adverse effects associated with metal implants in future.Trial registration: no human participant.