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| Názov: |
Inhibitory effect of ferroptosis inhibitor toxicity induced by cobalt nanoparticles through reactive oxygen species. |
| Alternate Title: |
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. (Chinese) |
| Autori: |
Wang Chen, Zhang Weinan, Shen Jining, Liu Fan, Yuan Jishan, Liu Yake |
| Zdroj: |
Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu; 12/8/2025, Vol. 29 Issue 34, p7310-7317, 8p |
| Predmety: |
TUMOR necrosis factors, ARTIFICIAL joints, METALS in surgery, NANOPARTICLE toxicity, REACTIVE oxygen species |
| Abstract (English): |
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 nanoparticlesinduced 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. [ABSTRACT FROM AUTHOR] |
| Abstract (Chinese): |
背景: 目前, 钴纳米颗粒引起的软组织损伤 是人工关节置换患者最常见的并发症之一。 因此, 需要一种有效的治疗策略来限制钴纳 米颗粒的毒性。 目的: 探讨铁死亡抑制剂对钴纳米颗粒诱导 细胞毒性的保护作用。 方法: 为评价铁死亡抑制剂对小鼠成纤维细 胞(Balb/3T3)的解毒作用, 以下实验均用钴 纳米颗粒和铁死亡抑制剂处理Balb/3T3细胞 24 h。细胞活力实验测定细胞存活率。根据 细胞活力实验结果确定钴纳米颗粒和去铁 酮浓度后, 将实验分为钴纳米颗粒处理组 (加入400 μmol/L钴纳米颗粒)、钴纳米颗粒+ 去铁酮共培养组(加入400 μmol/L钴纳米颗 粒和25 μmol/L去铁酮)、去铁酮处理组(加入 25 μmol/L去铁酮)及空白对照组。蛋白印迹 实验检测谷胱甘肽过氧化物酶4和溶质载体 家族7成员11蛋白的表达。 结果与结论: ①细胞活力实验结果显示, 随 着作用时间延长或药物浓度的增加, 细胞活 力会进一步降低, 表明钴纳米颗粒的细胞毒 性作用是时间和剂量依赖性的。此外, 暴露 24 h后, 与对照组相比, 钴纳米颗粒引起细 胞活力和谷胱甘肽水平显著降低(P < 0.05); 同时, 与对照组相比, 活性氧生成、细胞内 铁和炎症细胞因子如肿瘤坏死因子α、白细 胞介素1β和白细胞介素6表达量增加。加入 去铁酮后, 与钴纳米颗粒组相比, 细胞活力 明显提高, 活性氧生成、细胞内铁和炎症细 胞因子如肿瘤坏死因子α、白细胞介素1β和 白细胞介素6表达量也明显下降(P < 0.05)。 说明去铁酮对暴露于钴纳米颗粒的细胞有明 显的保护作用。②蛋白印迹实验结果显示, 钴纳米颗粒降低了谷胱甘肽过氧化物酶4和 溶质载体家族7成员11溶质载体家族7成员 11蛋白的表达(P < 0.05), 而去铁酮对此有抑 制作用(P < 0.05)。③上述结果证实, 钴纳米 颗粒具有很强的细胞毒性, 铁死亡抑制剂去 铁酮对钴纳米颗粒引起的细胞毒性有解毒作 用。铁死亡在钴纳米颗粒诱导细胞毒性的过 程中通过活性氧途径起重要作用。铁死亡抑 制剂对钴纳米颗粒毒性的抑制作用可能会有 助于进一步研究钴纳米毒性作用机制及解毒 方案。 [ABSTRACT FROM AUTHOR] |
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| Databáza: |
Complementary Index |
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