In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles

In vitro and in vivo evaluation of the toxicities induced by metallic nickel nano and fine particles
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金属镍纳米颗粒和细颗粒诱导毒性的体外和体内评价

DOI:
10.1007/s10735-016-9671-6
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发表时间:
2016-06-01
影响因子:
3.2
通讯作者:
Zhao, Jinshun
Zhao, Jinshun
中科院分区:
生物学4区
文献类型:
--
作者:
Magaye, Ruth;Gu, Yuanliang;Zhao, Jinshun

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随着纳米技术的快速发展,镍纳米颗粒(Ni NPs)已被应用于各个领域。然而,镍纳米粒子对健康的潜在不利影响尚不清楚。为了研究细胞和基因毒性并比较 Ni NP 和镍细颗粒 (Ni FP) 之间的差异,用不同剂量的 Ni NP 或 FP 处理 Sprague-Dawley (SD) 大鼠和 A549 细胞。气管内滴注Ni NPs和FPs对SD大鼠的肺、肝和肾造成急性毒性。尽管肺部组织学显示增生性改变,并且Western blot检测HO-1和Nrf2的蛋白表达显示肺负荷超负荷,但癌蛋白C-myc的表达水平没有观察到显着增加。细胞滴度-Glo 测定和彗星测定结果表明,Ni NPs 比 Ni FPs 更能引起体外细胞毒性和遗传毒性。此外,Ni NPs 在体外增加了 C-myc 的表达,但这些增加可能不是由于氧化应激,因为 HO-1 和 Nrf2 表达没有观察到显着的剂量依赖性变化。尽管 Ni NPs 有可能在体外引起 A549 细胞 DNA 损伤,但导致这些变化的分子机制及其致瘤潜力仍然存在争议。简而言之,Ni NPs 在体外引起细胞毒性和遗传毒性的能力比 Ni FPs 更强,并且气管内滴注 Ni NPs 和 FPs 对 SD 大鼠的器官产生毒性,而其表现出与两种颗粒类型相似的效果。这些结果表明,Ni NPs和FPs都有可能对人体健康有害,并且在相同的治疗剂量下,Ni NPs可能比Ni FPs具有更高的细胞和基因毒性作用。
Nickel nanoparticles (Ni NPs) have been applied in various fields along with the rapid development of nanotechnology. However, the potential adverse health effects of the Ni NPs are unclear. To investigate the cyto- and genotoxicity and compare the differences between the Ni NPs and the nickel fine particles (Ni FPs), Sprague-Dawley (SD) rats and A549 cells were treated with different doses of Ni NPs or FPs. Intra-tracheal instillation of Ni NPs and FPs caused acute toxicity in the lungs, liver and kidneys of the SD rats. Even though the histology of the lungs showed hyperplastic changes and the protein expression of HO-1 and Nrf2 detected by western blot showed lung burden overload, no significant increase was observed to the expression level of oncoprotein C-myc. The results from cell titer-Glo assay and comet assay indicated that Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs. In addition, Ni NPs increased the expression of C-myc in vitro, but these increases may not have been due to oxidative stress since no significant dose-dependent changes were seen in HO-1 and Nrf2 expressions. Although Ni NPs have the potential to cause DNA damage in A549 cells in vitro, the molecular mechanisms that led to these changes and their tumorigenic potential is still debatable. In short, Ni NPs were more potent in causing cell toxicity and genotoxicity in vitro than Ni FPs, and intra-tracheal instillation of Ni NPs and FPs caused toxicity in organs of the SD rats, while it showed similar to the effects for both particle types. These results suggested that both Ni NPs and FPs have the potential to be harmful to human health, and Ni NPs may have higher cyto- and genotoxic effects than Ni FPs under the same treatment dose.