Arsenic trioxide-induced cardiotoxicity triggers ferroptosis in cardiomyoblast cells

Area of Science:

• Cardiology
• Toxicology
• Cell Biology

Background:

• Arsenic trioxide (ATO) is effective for acute promyelocytic leukemia but causes cardiotoxicity.
• The mechanisms underlying ATO-induced cardiotoxicity are not fully understood.
• Ferroptosis is a potential, yet uninvestigated, mechanism for ATO-induced cardiotoxicity.

Purpose of the Study:

• To investigate the hypothesis that ferroptosis mediates ATO-induced cardiotoxicity.
• To evaluate the protective effects of the ferroptosis inhibitor ferrostain-1 (Fer-1) against ATO-induced cardiotoxicity in rat cardiomyocytes.

Main Methods:

• Rat cardiomyocyte H9c2 cells were treated with ATO.
• Ferrostain-1 (Fer-1) was administered 24 hours prior to ATO exposure.
• Cell death, apoptosis (Annexin V-APC/7-AAD assay), intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential, endoplasmic reticulum (ER) stress, and autophagy were assessed.

Main Results:

• ATO exposure induced significant H9c2 cell death and apoptosis.
• Pre-treatment with Fer-1 suppressed ATO-induced cell death and apoptosis.
• Fer-1 mitigated ATO-induced intracellular ROS production, loss of mitochondrial membrane potential, ER stress, and autophagy impairment.

Conclusions:

• ATO-induced cardiotoxicity may be mediated by ferroptosis.
• Ferrostain-1 demonstrates a cardioprotective effect against ATO-induced cellular injury.
• These findings suggest ferroptosis inhibitors as a potential therapeutic strategy for mitigating ATO cardiotoxicity.