Ferrostatin-1 and 3-Methyladenine Ameliorate Ferroptosis in OVA-Induced Asthma Model and in IL-13-Challenged BEAS-2B Cells

Oxid Med Cell Longev. 2022 Feb 4:2022:9657933. doi: 10.1155/2022/9657933. eCollection 2022.

Abstract

Ferroptosis was reported to be involved in the occurrence and development of asthma. However, the potential mechanism underlying the role of ferroptosis in asthma remains unclear. In this study, we established the mouse asthma model following the ovalbumin (OVA) method in C57BL/6 mice and the cell model with IL-13 induction in bronchial epithelial cells (BEAS-2B cells). Treatment of ferrostatin-1 (Ferr-1) and 3-methyladenine (3-MA) decreased iron deposition in IL-13-induced BEAS-2B cells and lung tissues of asthma mice, opposite to that in bronchoalveolar lavage fluid (BALF). Meanwhile, excessive lipid peroxidation asthma model in vivo and in vitro was alleviated by Ferr-1 or 3-MA treatment. In addition, Ferr-1 and 3-MA inhibited the expression of LC-3 in these cells and lung tissues of mice. Moreover, Ferr-1 and 3-MA also suppressed the production of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and oxidative stress factors (ROS and MDA), while promoting the level of SOD, in vivo and in vitro. Furthermore, application of Ferr-1 exhibited a greater inhibitory effect on iron release and lipid peroxidation in IL-13-induced BEAS-2B cells and asthma mice than 3-MA, accompanied with a weaker effect on ferritinophagy than 3-MA. Collectively, Ferr-1 and 3-MA ameliorated asthma in vivo and in vitro through inhibiting ferroptosis, providing a new strategy for the clinical treatment of asthma.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Animals
  • Asthma / chemically induced*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Bronchi / cytology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Line
  • Cyclohexylamines / administration & dosage*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Ferroptosis / drug effects*
  • Humans
  • Injections, Intraperitoneal
  • Interleukin-13 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / adverse effects*
  • Oxidative Stress / drug effects
  • Phenylenediamines / administration & dosage*
  • Signal Transduction / drug effects

Substances

  • Cyclohexylamines
  • Cytokines
  • Interleukin-13
  • Phenylenediamines
  • ferrostatin-1
  • 3-methyladenine
  • Ovalbumin
  • Adenine