Intratracheal Administration of Polystyrene Micro(nano)plastics with a Mixed Particle Size Promote Pulmonary Fibrosis in Rats by Activating TGF-β1 Signaling and Destabilizing Mitochondrial Dynamics and Mitophagy in a Dose- and Time-Dependent Manner.

BACKGROUND: Microplastics (MPs) can be inhaled by people. However, the relationships between long-term exposure to inhaled MPs, pulmonary fibrosis, and mitochondrial dysfunction are not completely clear. METHODS: SD rats were exposed to a 0.0125, 0.125, 0.31, or 1.25 mg/day dosage of mixed polystyrene MPs (PS-MPs), with the particle sizes ranging from 500 nm to 4 µm, via intratracheal administration, for 7 to 35 consecutive days. RESULTS: PS-MPs with particle sizes ranging from 1 µm to 4 µm were deposited in the lungs. The contents of NFκB-mediated proinflammatory cytokines were increased in the lungs of the rats after 7 days of PS-MP exposure. After exposure to PS-MPs, the degree of collagen deposition and the expression of TGF-β1/Smad increased significantly, and the levels of phosphorylated Akt (p-Akt) and nuclear β-catenin decreased significantly. The number of healthy mitochondria decreased, the expression of mitochondrial fission and fusion proteins increased, and the level of PINK1/Parkin-mediated mitophagy decreased in the lungs of the rats after 7 days of PS-MP exposure. A benchmark dose (BMD) of 0.151 mg/day and a benchmark dose lower confidence limit (BMDL) of 0.031 mg/day were identified on the basis of the subchronic effects of the intratracheal administration of the PS-MPs. CONCLUSIONS: Our study provides an in-depth understanding of the potential impacts of MP pollution on respiratory diseases.