Co-exposure of polystyrene nanoplastics and ozone synergistically induced airway inflammation: Evidence and biomarkers screening

Nanoplastics (NPs) or Ozone (O 3 ) is related to chronic respiratory diseases and can be exposed to human as coexisting air pollutants. However, there is no report on respiratory effect of co-exposure to NPs and O 3 . In this study, C57BL/6 J mice were instilled with polystyrene nanoplastics (PS-NPs, 1.82 ×10 11 , 3.64 ×10 11 ) intratracheally for 14 days and exposed with O 3 (0.6, 1.0 ppm, 3 h/d), lung function and pathological changes were determined, and the interaction between PS-NPs and O 3 on airway inflammation was calculated by factorial design analysis of variance and additive index. Then, transcriptomics and non-targeted metabolomics of lung tissue of mice were performed to screen the biomarkers. We found that co-exposure of PS-NPs and O 3 could synergistically induce airway inflammation in mice, with the severest injury in 1.00 O 3 + 1.82 × 10 11 PS-NPs group. Moreover, linoleic acid metabolism and ABC transporters were the key pathways, and the interaction of 3 core metabolites (prostaglandin F2b, 20-HETE, PLP) and 3 core genes (Per2, Per3 and cyp3a13) were significantly related to the occurrence of airway inflammation in mice. To our knowledge, this finding is the first to uncover the synergistical effect and biomarkers of co -exposure to PS-NPs and O 3 on airway inflammation.