SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Yong Heng Wang, Ning Li, Yi Guan, Tong Li, Yuxiu Zhang, Hong Cao, Zhi Hua Yu, Zhi Heng Li, Shuo Yan Li, Jia Hao Hu, Wen Xin Zhou, Si Si Qin, Shuang Li, San Qiao Yao
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Abstract

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model.

Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed.

Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO.

Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.

SiO 2 在硅肺病小鼠模型中诱导心肌细胞铁超载和铁突变。
研究目的本研究的目的是利用小鼠模型探讨铁变态反应在 SiO 2 诱导的心脏损伤中的作用和机制:方法:向雄性 C57BL/6 小鼠气管内灌入 SiO 2,建立矽肺模型。使用铁前列素-1(Fer-1)和去铁胺(DFO)抑制铁变态反应。对血清生物标志物、氧化应激标志物、组织病理学、铁含量和铁突变相关蛋白的表达进行了评估:结果:SiO 2 改变了血清心脏损伤生物标志物、氧化应激、铁积累和心肌组织中的铁变态标志物。Fer-1 和 DFO 降低了脂质过氧化和铁超载,减轻了 SiO 2 诱导的线粒体损伤和心肌损伤。SiO 2抑制了核因子红细胞2相关因子2(Nrf2)及其下游抗氧化基因,而与DFO相比,Fer-1能更有效地重新激活Nrf2:结论:铁超载诱导的铁变态反应是二氧化硅诱导的心脏损伤的原因之一。通过减少铁积累或抑制脂质过氧化来靶向铁变态反应,可防止 SiO 2 的心脏毒性,这可能是通过调节 Nrf2 通路实现的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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