Inhalation Toxicology Center for Airborne Risk Factor, Korea Institute of Toxicology, 30 Baehak1-gil, Jeongeup, Jeollabuk-do, 56212, Republic of Korea.
Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan-Si, Jeollabuk-do, Republic of Korea.
Part Fibre Toxicol. 2023 Jan 10;20(1):2. doi: 10.1186/s12989-022-00512-8.
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.
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.
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.
聚丙烯(PP)用于各种产品,如一次性容器、勺子和汽车零件。用于 COVID-19 预防的一次性口罩主要由 PP 制成,由于潜在的环境污染,这些口罩的处理令人担忧。最近的报告表明,风化的 PP 微颗粒可能被吸入,但 PP 微颗粒的吸入毒理学知之甚少。
与对照组相比,2.5 或 5mg/kg PP 注入小鼠的炎症细胞数量、活性氧(ROS)产生以及炎症细胞因子和趋化因子水平显著增加。PP 刺激小鼠的肺组织组织病理学分析显示肺损伤,包括血管周围/实质空间的炎症细胞浸润、肺泡上皮细胞增生和泡沫状巨噬细胞聚集。体外研究表明,PP 刺激导致线粒体功能障碍,包括线粒体去极化和三磷酸腺苷(ATP)水平降低。PP 刺激导致 A549 细胞的细胞毒性、ROS 产生、炎症细胞因子增加和细胞死亡。结果表明,PP 刺激在体内和体外均增加了 p-p38 和 p-NF-κB 蛋白水平,而 p-ERK 和 p-JNK 保持不变。有趣的是,A549 细胞中 p38 和 ROS 抑制调节了由 PP 暴露引起的细胞毒性。
这些结果表明,PP 刺激可能通过线粒体损伤导致的 p38 磷酸化介导的 NF-κB 途径导致炎症发病机制。