SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
- Author:
Wang YONGHENG
1
,
2
;
Li NING
;
Guan YI
;
LI TONG
;
Zhang YUXIU
;
Cao HONG
;
Yu ZHIHUA
;
Li ZHIHENG
;
Li SHUOYAN
;
Hu JIAHAO
;
Zhou WENXIN
;
Qin SISI
;
Li SHUANG
;
Yao SANQIAO
Author Information
- Keywords: SiO2 exposure; Iron overload; Ferroptosis; Cardiac injury; Nrf2
- From: Biomedical and Environmental Sciences 2024;37(6):617-627
- CountryChina
- Language:Chinese
- Abstract: Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 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 SiO2 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 SiO2-induced mitochondrial damage and myocardial injury.SiO2 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 SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
