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.

Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. To investigate the effects of PPD exposure on the risk of allergic asthma, we established a PPD exposure group in a mouse model. The dose administered for PS-MP was 0.1 mg/d and for DBP was 30 mg/kg/d, with a 5-week oral administration period. The pathological changes of airway tissue and the increase of oxidative stress and inflammatory response confirmed that PPD aggravated eosinophilic allergic asthma in mice. The mitochondrial morphological changes and metabolomics of mice confirmed that ferrotosis and oxidative stress played key roles in this process. Treatment with 100 mg/Kg deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological. Our findings suggest that 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. In this study, the molecular mechanism by which PPD aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PPD and lays a theoretical foundation for addressing the health risks posed by PPD.

Prenatal co-exposure to diisodecyl phthalate and ozone contribute to depressive behavior in offspring mice through oxidative stress and TWIST1 participation.

Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.