Ferrostatin-1 alleviates cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis

Bioengineered

Fan Liu¹  Yake Liu¹  Weinan Zhang¹  Chen Wang¹  Wenfeng Zhu² 

[1] Affiliated Hospital of Nantong University;The Sixth Affiliated Hospital of Nantong University;

关键词: cobalt nanoparticles;    ferroptosis;    ferrostatin-1;    hip arthroplasty;    lipid peroxidation;   

DOI  :  10.1080/21655979.2022.2042143

来源: DOAJ

【 摘 要 】

Cobalt is the main component of metal prostheses in hip arthroplasty. Studies have shown that metal particles mainly composed of cobalt nanoparticles (CoNPs) can cause systemic and local toxic reactions due to various physical and chemical factors. Therefore, elucidating the underlying mechanisms of metal prosthesis action, coupled with identification of effective detoxification drugs are imperative to minimizing postoperative complications and prolonging the service life of these clinical tools. In this study, we treated Balb/3T3 mouse fibroblast cell line with CoNPs and ferrostatin-1, then measured cell viability via the CCK-8 assay. Next, we determined levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), cobalt and iron contents, as well as glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) expression in each group. Finally, we employed transmission electron microscopy (TEM) to detect changes in the ultrastructure of each group of cells. Exposure of cells to CoNPs significantly suppressed their viability, and downregulated expression of GSH, GPX4, and SLC7A11 proteins. Conversely, this treatment mediated a significant increase in ROS, MDA, cobalt, and iron levels in the cells. TEM images revealed a marked increase in density of the mitochondrial membrane of cells in the CoNPs group, while the outer membrane was broken. Notably, treatment with ferroptosis inhibitor Ferrostatin-1 alleviated the cytotoxic response caused by CoNPs. These findings suggest that CoNP-induced cytotoxicity may be closely related to ferroptosis, indicating that inhibition of ferroptosis is a potential therapeutic strategy for reducing CoNP toxicity.

【 授权许可】

Unknown