Mechanisms of Exacerbation of Th2-Mediated Eosinophilic Allergic Asthma Induced by Plastic Pollution Derivatives (Ppd): A Molecular Toxicological Study Involving Lung Cell Ferroptosis and Metabolomics

Abstract

Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. In this study, we developed a concise exposure model to examine the impact of PPD exposure on allergic asthma risk by co-exposing PS-MP and DBP. Using a mouse model of allergic asthma, we assessed airway inflammation, hyperresponsiveness, and type I hypersensitivity. Our findings suggest that PPD exposure exacerbates allergic asthma in mice, with ferroptosis and oxidative stress playing key roles in this worsening. The increased levels of reactive oxygen species (ROS) in the lungs lead to Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-5, and eosinophils, and reduced INF-γ levels. This inflammatory response is mediated by the NFκB pathway and exacerbates type I hypersensitivity through increased IL-4 production. Treatment with deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological.

Note:
Funding Information: This work was supported by the National Natural Science Foundation of China (42177416, 52278090), Key Special Project for Social Development R&D of Xianning City Science and Technology Program (2021SFYF007, 2023SFYF095), and Scientific Research Innovative Team of Hubei University of Science and Technology (2023T08).

Declaration of Interests: The authors declare that they have no competing interest.

Ethics Approval Statement: This experiment was supervised and approved by the Ethics Committee of Hubei University of Science and Technology (ID: HBUST-IACUC-2021–010).

Keywords: Plastic pollution derivatives (PPD), Allergic asthma, Ferroptosis, Oxidative stress, NFκB pathway, Metabolomics analysis