2. Academic Validation
  3. Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice

Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice

  • Ecotoxicol Environ Saf. 2023 Jul 20;263:115279. doi: 10.1016/j.ecoenv.2023.115279.
Liang Xiong 1,  Jinyu Huang 2,  Chunmei Wu 3,  Qiong Yuan 4,  Sihui Wang 4,  Liye Zhu 4,  Zilu Li 3,  Ziyue Sun 3,  Yi Fang 3,  Weisong Li 5,  Gonghua Hu 6
Affiliations

Affiliations

  • 1 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Key Laboratory of Environment and Health of Ganzhou, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China.
  • 2 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China.
  • 3 School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China.
  • 4 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China.
  • 5 Department of Pathology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China.
  • 6 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Key Laboratory of Environment and Health of Ganzhou, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China. Electronic address: [email protected].
PMID: 37480692 DOI: 10.1016/j.ecoenv.2023.115279
Abstract

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers Ferroptosis through the Glutathione Peroxidase 4 (GPX4)/glutathione (GSH)/system Xc- axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in Ferroptosis and lipid metabolism-related pathways were enriched. The Ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.

Keywords

Cardiac dysfunction; Ferroptosis; Inflammation; Lipid peroxide; Yttrium.

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