Department of Toxicity and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, People's Republic of China.
Beijing Key Laboratory of Environmental Toxicity, Capital Medical University, Beijing, 100069, People's Republic of China.
Environ Sci Pollut Res Int. 2017 Dec;24(36):27767-27777. doi: 10.1007/s11356-017-0228-3. Epub 2017 Oct 5.
The co-exposure toxicity mechanism of ultrafine particles and pollutants on human cardiovascular system are still unclear. In this study, the combined effects of silica nanoparticles (SiNPs) and/or carbon black nanoparticles (CBNPs) with Pb(AC) compared with particulate matter (PM) were investigated in human myocardial cells (AC16). Our study detected three different combinations of SiNPs and Pb(AC), CBNPs and Pb(AC), and SiNPs and CBNPs compared with PM at low-dose exposure. Using PM as positive control, our results suggested that the combination of SiNPs and Pb(AC)/CBNPs could increase the production of reactive oxygen species (ROS), lactate dehydrogenase leakage (LDH), and malondialdehyde (MDA) and decrease the activities of superoxide dismutase (SOD) and glutathione (GSH); induce inflammation by the upregulation of protein CRP and TNF-α, and apoptosis by the upregulation of protein caspase-3, caspase-9, and Bax while the downregulation of protein Bcl-2; and trigger G2/M phase arrest by the upregulation of protein Chk2 and downregulation of protein Cdc2 and cyclin B1. In addition, the combination of CBNPs and Pb(AC) induced a significant increase in MDA and reduced the activities of ROS, LDH, SOD, and GSH, with G1/S phase arrest via upregulation of Chk1 and downregulation of CDK6 and cyclin D1. Our data suggested that the additive interaction and synergistic interaction are the major interaction in co-exposure system, and PM could trigger more severe oxidative stress, G2/M arrest, and apoptosis than either co-exposure or single exposure.
超细颗粒和污染物对人体心血管系统的共暴露毒性机制尚不清楚。在这项研究中，与颗粒物（PM）相比，研究人员在人心肌细胞（AC16）中检测了二氧化硅纳米颗粒（SiNPs）和/或碳黑纳米颗粒（CBNPs）与 Pb（AC）的三种不同组合的联合效应。我们的研究检测了 SiNPs 和 Pb(AC)、CBNPs 和 Pb(AC)以及 SiNPs 和 CBNPs 与低剂量暴露的 PM 的三种不同组合。使用 PM 作为阳性对照，我们的结果表明，SiNPs 和 Pb(AC)/CBNPs 的组合可能会增加活性氧物质 (ROS)、乳酸脱氢酶漏出 (LDH)和丙二醛 (MDA)的产生，并降低超氧化物歧化酶 (SOD)和谷胱甘肽 (GSH)的活性；通过上调 CRP 和 TNF-α 蛋白引起炎症，通过上调蛋白 caspase-3、caspase-9 和 Bax 以及下调蛋白 Bcl-2 引起细胞凋亡；通过上调 Chk2 蛋白和下调 Cdc2 和 cyclin B1 蛋白引发 G2/M 期阻滞。此外，CBNPs 和 Pb(AC)的组合会导致 MDA 显著增加，降低 ROS、LDH、SOD 和 GSH 的活性，并通过上调 Chk1 和下调 CDK6 和 cyclin D1 导致 G1/S 期阻滞。我们的数据表明，共暴露系统中的主要相互作用是加性相互作用和协同相互作用，与单一暴露或共暴露相比，PM 可能会引发更严重的氧化应激、G2/M 期阻滞和细胞凋亡。
