SiO_(2) Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model  

作　　者：Yongheng Wang Ning Li Yi Guan Tong LI Yuxiu Zhang Hong Cao Zhihua Yu Zhiheng Li Shuoyan Li Jiahao Hu Wenxin Zhou Sisi Qin Shuang Li Sanqiao Yao 

机构地区：[1]School of Public Health,North China University of Science and Technology,Tangshan 063210,Hebei,China [2]Hebei Key Laboratory of Occupational Health and Safety for Coal Industry,North China University of Science and Technology,Tangshan 063210,Hebei,China [3]Occupational Disease Prevention and Control Institute of Jinneng Holding Coal Industry Group Co.,Ltd,Datong 037001,Shanxi,China [4]China Pingmei Shenma Group Occupational Disease Prevention and Control Hospital,Pingdingshan 467000,Henan,China [5]School of Public Health,Xinxiang Medical University,Xinxiang 453003,Henan,China

出　　处：《Biomedical and Environmental Sciences》2024年第6期617-627,共11页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Science Foundation of China[No.U21A20334,82373544];Hebei Provincial Department of Science and Technology Centrally Guided Local Development Fund Project[236Z7705G];Occupational health risk assessment and the formulation of national occupational health standards[102393220020090000020].

摘　　要：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.

关 键 词：SiO_(2) exposure Iron overload Ferroptosis Cardiac injury NRF2 

分 类 号：R135.2[医药卫生—劳动卫生]