2. Academic Validation
  3. Vitamin C alleviates PM2.5-induced thyroid injury and ferroptosis by regulating the IL-17A/IL-17RA/ACT1 signaling pathway

Vitamin C alleviates PM2.5-induced thyroid injury and ferroptosis by regulating the IL-17A/IL-17RA/ACT1 signaling pathway

  • Ecotoxicol Environ Saf. 2025 Aug 2:303:118796. doi: 10.1016/j.ecoenv.2025.118796.
Xinwen Dong 1,  Xiaofeng Han 2,  Jie Gao 3,  Cuiying Li 4,  Zheng Luo 5,  Zhaoxue Zhu 6,  Yaguang Su 7,  Sanqiao Yao 8,  Fengquan Zhang 9,  Jie Xu 10,  Li Zhang 11,  Haibin Li 12,  Chenguang Zhang 13,  Weidong Wu 14
Affiliations

Affiliations

  • 1 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: dongxinwen118@yeah.net.
  • 2 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 50220102001@stu.xxmu.edu.cn.
  • 3 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 13721740611@163.com.
  • 4 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 13849183139@163.com.
  • 5 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: lz15603741558@163.com.
  • 6 School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 15736905191@163.com.
  • 7 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 50220209007@stu.xxmu.edu.cn.
  • 8 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 131059@xxmu.edu.cn.
  • 9 Experimental Teaching Center of Public Health and Preventive Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: zhangfengquan29@126.com.
  • 10 Experimental Teaching Center of Public Health and Preventive Medicine, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: sunny224802@163.com.
  • 11 Center for Bioinformatics and Statistical Health Research, School of Public Health, Xinxiang Medical, Xinxiang, Henan Province 453003, China. Electronic address: zhangli@xxmu.edu.cn.
  • 12 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: Lihaibin@xxmu.edu.cn.
  • 13 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: 328151081@qq.com.
  • 14 Department of Environmental and Occupational Health, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China. Electronic address: wuwridong@xxmu.edu.cn.
PMID: 40753780 DOI: 10.1016/j.ecoenv.2025.118796
Abstract

Fine particulate matter (PM2.5) is a ubiquitous environmental pollutant that has been demonstrated to affect the thyroid function in women. However, its specific mechanism remains unclear, and protective drugs are deficient. In the present study, we used female rat thyroid models in vivo and rat FRTL5 cell models in vitro to investigate the thyroid toxicity mechanism of PM2.5 and the protective pathway of vitamin C in female rats. PM2.5 exposure caused the production of inflammatory cells in thyroid tissue; transformations of the mitochondrial morphology; increases in the Reactive Oxygen Species (ROS), ferrous ion (Fe2 +), and malondialdehyde (MDA) content in thyroid cells; and decreases in the Glutathione Peroxidase 4 (GPX4) levels, which resulted in Ferroptosis in rat thyroid tissues. In addition, the Interleukin (IL)-17A/IL-17RA/Nuclear factor activator (Act1) signaling pathway was activated by PM2.5. However, vitamin C treatment improved Ferroptosis and significantly reduced the expression of the IL-17A, IL-17RA, and ACT1 signaling pathway-related factors. These findings indicate that vitamin C demonstrates protective effects against thyroid injury and Ferroptosis, potentially through the inhibition of the IL-17A signaling pathway.

Keywords

Ferroptosis; IL-17A signaling pathway; PM(2.5); Thyroid; Vc.

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