2. Academic Validation
  3. Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach

Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach

  • J Hazard Mater. 2024 Dec 5:480:135814. doi: 10.1016/j.jhazmat.2024.135814.
Yuanjin Chang 1,  Xiaofan Jiang 1,  Jianrui Dou 2,  Ruijin Xie 3,  Wenjing Zhao 4,  Yingsi Cao 1,  Ju Gao 4,  Fanglong Yao 4,  Dongqin Wu 1,  Huiya Mei 1,  Yanqi Zhong 5,  YuXi Ge 5,  Hua Xu 1,  Wenjun Jiang 1,  Xue Xiao 1,  Yuanying Jiang 6,  Shudong Hu 7,  Yu Wu 8,  Yueying Liu 9
Affiliations

Affiliations

  • 1 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China.
  • 2 Department of Occupational Safety and Health, Center for Disease Control and Prevention of Yangzhou, Yangzhou, China.
  • 3 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China; Yangzhou Polytechnic College, Yangzhou, China.
  • 4 Yangzhou Key Laboratory of Anesthesiology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
  • 5 Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, China.
  • 6 Linping Campus, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 7 Department of Radiology, Affiliated Hospital of Jiangnan University, Wuxi, China. Electronic address: hsd2001054@163.com.
  • 8 Lab of Modern Environmental Toxicology, Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China. Electronic address: wuyu@jiangnan.edu.cn.
  • 9 Department of Pediatrics, Affiliated Hospital of Jiangnan University, Wuxi, China. Electronic address: shadow7671@163.com.
PMID: 39303606 DOI: 10.1016/j.jhazmat.2024.135814
Abstract

Cadmium, a toxic heavy metal from industrial activities, poses a neurotoxic risk, especially to children. While seizures are common in children, the link between cadmium and seizure activity is unclear. Ferroptosis, an iron-dependent cell death, is key in seizure-induced hippocampal damage and related anxiety. This study aims to elucidate these mechanisms and assess the broader implications of cadmium exposure. Our research contributes in three significant areas: Firstly, through a combination of observational studies in long-term cadmium-exposed workers, Mendelian randomization analysis, NHANES analysis, urinary metabolomics, and machine learning analysis, we explored the impact of long-term cadmium exposure on inflammatory cytokines, ferroptosis-related gene expression, and lipid and iron metabolism. Secondly, by harnessing public databases for human disorders and metal-associated gene targets, alongside therapeutic molecular analyses, we identified critical human gene targets for cadmium toxicity in seizures and proposed melatonin as a promising therapeutic agent. Finally, utilizing mouse behavioral assays, T2 MRI, and MRS, we provide evidence of how prolonged cadmium exposure disrupts iron and lipid metabolism in the brain, triggering Ferroptosis in the hippocampus.

Keywords

Bioinformatics analysis; Cadmium; Ferroptosis; Seizures.

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