SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model

Biomed Environ Sci. 2024 Jun 20;37(6):617-627. doi: 10.3967/bes2024.087.

Abstract

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.

Keywords: Cardiac injury; Ferroptosis; Iron overload; Nrf2; SiO2 exposure.

MeSH terms

  • Animals
  • Cyclohexylamines / pharmacology
  • Deferoxamine / pharmacology
  • Disease Models, Animal*
  • Ferroptosis* / drug effects
  • Iron / metabolism
  • Iron Overload* / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Myocytes, Cardiac* / drug effects
  • Myocytes, Cardiac* / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Phenylenediamines / pharmacology
  • Silicon Dioxide* / toxicity
  • Silicosis* / drug therapy
  • Silicosis* / metabolism
  • Silicosis* / pathology

Substances

  • Silicon Dioxide
  • Deferoxamine
  • Phenylenediamines
  • ferrostatin-1
  • NF-E2-Related Factor 2
  • Iron
  • Cyclohexylamines