Inhibitory effect of ferroptosis inhibitor toxicity induced by cobalt nanoparticles through reactive oxygen species
- VernacularTitle:铁死亡抑制剂通过活性氧途径对钴纳米颗粒毒性的抑制作用
- Author:
Chen WANG
1
;
Weinan ZHANG
;
Jining SHEN
;
Fan LIU
;
Jishan YUAN
;
Yake LIU
Author Information
- Publication Type:Journal Article
- Keywords: cobalt nanoparticle; arthroplasty; ferroptosis inhibitor; ferroptosis; reactive oxygen species; deferiprone; metal implant; detoxify; nanobiomedicine; pathway; fibroblast
- From: Chinese Journal of Tissue Engineering Research 2025;29(34):7310-7317
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.
