Sthijns Mireille M J P E, Thongkam Waluree, Albrecht Catrin, Hellack Bryan, Bast Aalt, Haenen Guido R M M, Schins Roel P F
Department of Pharmacology and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 DE Düsseldorf, Germany.
Toxicol In Vitro. 2017 Apr;40:223-233. doi: 10.1016/j.tiv.2017.01.010. Epub 2017 Jan 18.
Despite the gaps in our knowledge on the toxicity of silver nanoparticles (AgNPs), the application of these materials is fast expanding, from medicine, to food as well as the use in consumer products. It has been reported that prolonged exposure might make cells more resistant to AgNPs. This prompted us to investigate if AgNPs may give rise to a hormetic response. Two types of AgNPs were used, i.e. colloidal AgNPs and an AgNP powder. For both types of nanosilver it was found that a low dose pretreatment of A549 human epithelial cells with AgNPs induced protection against a toxic dose of AgNPs and acrolein. This protection was more pronounced after pretreatment with the colloidal AgNPs. Interestingly, the mechanism of the hormetic response appeared to differ from that of acrolein. Adaptation to acrolein is related to Nrf2 translocation, increased mRNA expression of γGCS, HO-1 and increased GSH levels and the increased GSH levels can explain the hormetic effect. The adaptive response to AgNPs was not related to an increase in mRNA expression of γGCS and GSH levels. Yet, HO-1 mRNA expression and Nrf2 immunoreactivity were enhanced, indicating that these processes might be involved. So, AgNPs induce adaptation, but in contrast to acrolein GSH plays no role.
尽管我们对银纳米颗粒（AgNPs）毒性的了解存在差距，但这些材料的应用正在迅速扩展，从医学领域到食品以及消费品的使用。据报道，长期接触可能会使细胞对AgNPs更具抗性。这促使我们研究AgNPs是否会引起兴奋效应。使用了两种类型的AgNPs，即胶体AgNPs和AgNP粉末。对于这两种类型的纳米银，发现用AgNPs对A549人上皮细胞进行低剂量预处理可诱导对毒性剂量的AgNPs和丙烯醛的保护作用。用胶体AgNPs预处理后，这种保护作用更为明显。有趣的是，兴奋效应的机制似乎与丙烯醛不同。对丙烯醛的适应与Nrf2易位、γGCS、HO-1的mRNA表达增加以及GSH水平升高有关，而GSH水平升高可以解释兴奋效应。对AgNPs的适应性反应与γGCS的mRNA表达和GSH水平的增加无关。然而，HO-1 mRNA表达和Nrf2免疫反应性增强，表明这些过程可能参与其中。因此，AgNPs诱导适应，但与丙烯醛不同，GSH不起作用。
