Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
Animal Science Department, NC Research Campus Kannapolis, Plants for Human Health Institute, 600 Laureate Way, Kannapolis, NC, 28081, USA.
Environ Sci Pollut Res Int. 2020 Sep;27(25):31841-31853. doi: 10.1007/s11356-020-09412-w. Epub 2020 Jun 5.
The lungs are one the main organs exposed to environmental pollutants, such as tropospheric ozone (O) and particulate matter (PM), which induce lung pathologies through similar mechanisms, resulting in altered redox homeostasis and inflammation. Although numerous studies have investigated the effects of these pollutants in the respiratory tract, there are only a few evidences that have evaluated the combined effects of outdoor stressors, despite the fact that humans are consistently exposed to more pollutants simultaneously. In this study, we wanted to investigate whether exposure to PM and O could have an additive, noxious effect in lung epithelial cells by measuring oxidative damage and the activity of redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2) which is a master regulator of cellular antioxidant defenses. First, we measured the cytotoxic effects of O and PM individually and in combination. We observed that both pollutants alone increased LDH release 24 h post-exposure. Interestingly, we did observe via TEM that combined exposure to O and PM resulted in increased cellular penetration of PM particles. Furthermore, we found that levels of 4-hydroxy-nonenal (4HNE), a marker of oxidative damage, significantly increased 24 h post-exposure, in response to the combined pollutants. In addition, we observed increased levels of Nrf2, in response to the combined pollutants vs. either pollutant, although this effect was not followed by the increase in Nrf2-responsive genes expression HO1, SOD1, GPX, or GR nor enzymatic activity. Despite these observations, our study suggests that O exposure facilitate the cellular penetration of the particles leading to an increased oxidative damage, and additive defensive response.
肺部是暴露于环境污染物（如对流层臭氧 (O) 和颗粒物 (PM)）的主要器官之一，这些污染物通过相似的机制诱导肺部病变，导致氧化还原稳态和炎症改变。尽管许多研究已经调查了这些污染物在呼吸道中的影响，但只有少数证据评估了户外应激源的联合影响，尽管事实上人类一直在同时暴露于更多的污染物中。在这项研究中，我们想通过测量氧化损伤和氧化还原敏感核因子红细胞 2 相关因子 2 (Nrf2) 的活性来研究 PM 和 O 暴露是否会对肺上皮细胞产生相加的有害影响，Nrf2 是细胞抗氧化防御的主要调节剂。首先，我们单独和组合测量了 O 和 PM 的细胞毒性作用。我们观察到，两种污染物单独作用都会增加 24 小时后 LDH 的释放。有趣的是，我们通过 TEM 观察到，O 和 PM 的联合暴露会导致 PM 颗粒更深入地穿透细胞。此外，我们发现，氧化损伤标志物 4-羟基壬烯醛 (4HNE) 的水平在联合污染物暴露后 24 小时显著增加，而与单独的污染物相比。此外，我们观察到 Nrf2 的水平增加，与联合污染物相比，与任何一种污染物相比，尽管这一效应并没有伴随着 Nrf2 反应性基因表达 HO1、SOD1、GPX 或 GR 或酶活性的增加。尽管有这些观察结果，但我们的研究表明，O 暴露会促进颗粒的细胞穿透，导致氧化损伤增加，并产生相加的防御反应。
