Ferroptosis participates in dibutyl phthalate-aggravated allergic asthma in ovalbumin-sensitized mice.

Abstract

Dibutyl phthalate (DBP), used as a plasticizer, is of wide concern as an environmental pollutant since it has certain immunotoxicity. Although there is growing evidence supporting a link between DBP exposure and allergic airway inflammation, there is less information concerned with whether the ferroptosis pathway is involved in DBP-aggravated allergic asthma in ovalbumin (OVA)-sensitized mice. This study aimed to investigate the role and underlying mechanisms of ferroptosis in DBP-exposed allergic asthmatic mice. Balb/c mice were orally exposed to 40 mg/kg-1 DBP for 28 days, followed by sensitization with OVA and seven consecutive challenges with nebulized OVA. We analyzed airway hyperresponsiveness (AHR), immunoglobulins, inflammation and pulmonary histopathology, to investigate whether DBP exacerbates allergic asthma in OVA-induced mice. We also measured the biomarkers of ferroptosis (Fe2+, GPX4, PTGS2), proteins related to the ferroptosis pathway (VEGF, IL-33, HMGB1, SLC7A11, ALOX15, PEBP1), and indices of lipid peroxidation (ROS, Lipid ROS, GSH, MDA, 4-HNE), to explore the role of ferroptosis in DBP+OVA mice. Finally, we used ferrostatin-1 (Fer-1) as an antagonist against the harmful effects of DBP. The results showed that, DBP+OVA mice had a significant increase in AHR, airway wall remodeling and airway inflammation. Further, we showed that DBP aggravated allergic asthma via ferroptosis and lipid peroxidation, and that Fer-1 inhibited ferroptosis and alleviated the pulmonary toxicity of DBP. These results suggest that ferroptosis participates in the exacerbation of allergic asthma resulting from oral exposure to DBP, highlighting a novel pathway for the connection between DBP and allergic asthma.

• Authors: Yan Li, Biao Yan, Yang Wu, Qi Peng, Yaolu Wei, Yenan Chen, Yuping Zhang, Ning Ma, Xu Yang, Ping Ma
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 256 Pg. 114848 (May 2023) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 37018853 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Ovalbumin
• Dibutyl Phthalate
• Reactive Oxygen Species

Topics

• Animals
• Mice
• Ovalbumin (adverse effects)
• Dibutyl Phthalate
• Ferroptosis
• Reactive Oxygen Species
• Asthma (chemically induced)
• Hypersensitivity
• Lung
• Inflammation
• Mice, Inbred BALB C