Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage

Abstract

Background Polypropylene (PP) is used in various products such as disposable containers, spoons, and automobile parts. The disposable masks used for COVID-19 prevention mainly comprise PP, and the disposal of such masks is concerning because of the potential environmental pollution. Recent reports have suggested that weathered PP microparticles can be inhaled, however, the inhalation toxicology of PP microparticles is poorly understood. Results Inflammatory cell numbers, reactive oxygen species (ROS) production, and the levels of inflammatory cytokines and chemokines in PP-instilled mice (2.5 or 5 mg/kg) increased significantly compared to with those in the control. Histopathological analysis of the lung tissue of PP-stimulated mice revealed lung injuries, including the infiltration of inflammatory cells into the perivascular/parenchymal space, alveolar epithelial hyperplasia, and foamy macrophage aggregates. The in vitro study indicated that PP stimulation causes mitochondrial dysfunction including mitochondrial depolarization and decreased adenosine triphosphate (ATP) levels. PP stimulation led to cytotoxicity, ROS production, increase of inflammatory cytokines, and cell deaths in A549 cells. The results showed that PP stimulation increased the p-p38 and p-NF-κB protein levels both in vivo and in vitro, while p-ERK and p-JNK remained unchanged. Interestingly, the cytotoxicity that was induced by PP exposure was regulated by p38 and ROS inhibition in A549 cells. Conclusions These results suggest that PP stimulation may contribute to inflammation pathogenesis via the p38 phosphorylation-mediated NF-κB pathway as a result of mitochondrial damage.

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice

“…Ten micrograms per liter of 70 μm PP-MP significantly reduced the survival rate of zebrafish [ 40 ]. However, few studies have measured the effects of PP-MPs on mammalian and cell models, although PP-MPs contribute to pulmonary inflammation in vivo and affect the level of immune cytokines in vitro [ 41 , 42 ]. Meanwhile, PP-MPs with an average particle size of > 50 μm do not exhibit acute toxicity in rats [ 43 , 44 , 45 ].…”

Elucidating the effects of naturally weathered aged-polypropylene microplastics and newly procured polypropylene microplastics on raw 264.7 macrophages

“…Accordingly, in another experiment, the ROS production in the mitochondria of A549 cells exposed to 4 mg mL −1 PP (252 nm) significantly increased when compared to the control. 92 Microplastics undergoing weathering in the environment can alter their physicochemical characteristics and subsequent biological behaviours. 93 The conversion of plastic products to MPs exacerbates the harmful effects within cells, increases their surface-to-mass ratio, and allows them to migrate through lipid membranes into the cells.…”

Chlorogenic Acid Alleviates Chronic Stress-Induced Intestinal Damage by Inhibiting the P38MAPK/NF-κB Pathway

“…ERK and JNK were unchanged after chronic stress or CGA treatment. p38MAPK is an important member of MAPK, which is not only involved in the cell cycle, development, differentiation, cell death, senescence, and tumorigenesis, but also acts as a specific serine/threonine kinase to regulate inflammation. , A large number of studies have shown that p38 could activate the NF-κB signaling pathway, thereby causing inflammation in some diseases such as IBD, alcohol-induced hepatic injury, lung inflammation, and Parkinson’s. − After SB203580 intervention, the phosphorylation level of p65 was significantly reduced, and the transcription and translation levels of TNF were significantly reduced. The intestinal damage was also significantly reduced.…”