Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, China.
Cancer Epidemiology Program, University of Hawaii Cancer Center, USA.
J Toxicol Sci. 2020;45(3):117-129. doi: 10.2131/jts.45.117.
Silica nanoparticles (SiO NPs) are widely used in daily life and can enter organisms through several pathways, often causing unpredictable toxicity. Although SiO NPs are known to cause damage to the respiratory system, little is known about their oral toxicity, and their potential harm to the reproductive system is unclear. In this study, we used a Caenorhabditis elegans model to clarify SiO NPs oral toxicity in vivo and explore their effect on the reproductive system. We exposed C. elegans to 0.25, 0.5 and 1 mg /mL SiO NPs for 24 hr. Our results showed that SiO NPs exposure for 24 hr did not affect nematode survival rates, but did affect, to varying degrees, the reproduction, development, and movement of nematodes, with nematode fecundity being the most sensitive to SiO NPs toxicity. The NPs exposed group showed enhanced germ cell apoptosis and increased oxidative stress as seen through an increase in ROS and malondialdehyde (MDA), and decrease in reduced glutathione (GSH). N-acetyl-L-cysteine (NAC), an antioxidant, negated SiO NPs effect on germ cells and restored nematodes reproductive ability. We also found that SiO NPs could affect the expression of genes related to metal detoxification, oxidative stress, and apoptosis. The expression of metallothionein coding genes mtl-1 and mtl-2 changed most significantly among the tested genes. We demonstrated that SiO NPs could enhance germ cell apoptosis by inducing oxidative stress, providing a new area for studies of the mechanism of SiO NP toxicity.
硅纳米颗粒(SiO NPs)在日常生活中被广泛应用,它们可以通过多种途径进入生物体,常常导致不可预测的毒性。虽然已知 SiO NPs 会对呼吸系统造成损害,但对于其口服毒性知之甚少,其对生殖系统的潜在危害也不清楚。在这项研究中,我们使用秀丽隐杆线虫模型来阐明 SiO NPs 的体内口服毒性,并探索其对生殖系统的影响。我们将秀丽隐杆线虫暴露于 0.25、0.5 和 1mg/mL 的 SiO NPs 中 24 小时。结果表明,SiO NPs 暴露 24 小时不会影响线虫的存活率,但会不同程度地影响线虫的繁殖、发育和运动,线虫的繁殖力对 SiO NPs 毒性最为敏感。NP 暴露组表现出增强的生殖细胞凋亡,并通过增加 ROS 和丙二醛(MDA)以及降低还原型谷胱甘肽(GSH)来增加氧化应激。抗氧化剂 N-乙酰-L-半胱氨酸(NAC)消除了 SiO NPs 对生殖细胞的影响,并恢复了线虫的生殖能力。我们还发现,SiO NPs 可以影响与金属解毒、氧化应激和细胞凋亡相关的基因的表达。在测试的基因中,金属硫蛋白编码基因 mtl-1 和 mtl-2 的表达变化最为显著。我们证明,SiO NPs 可以通过诱导氧化应激来增强生殖细胞凋亡,为研究 SiO NP 毒性的机制提供了新的领域。