Effects of Silver Nanoparticles on the Liver and Hepatocytes In Vitro
Effects of Silver Nanoparticles on the Liver and Hepatocytes In Vitro
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DOI：
10.1093/toxsci/kfs306
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发表时间：
2013-02-01
影响因子：
3.8
通讯作者：
Stone, Vicki
中科院分区：
文献类型：
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作者：
Gaiser, Birgit K.;Hirn, Stephanie;Stone, Vicki
随着纳米颗粒 (NP) 的使用和融入消费产品的增加，有必要筛查潜在毒性以确保客户安全。纳米颗粒已被证明在吸入和摄入后会转移到血流中，此类研究表明肝脏是一个重要的积累器官。银 (Ag) 纳米颗粒由于用于食品接触材料、膳食补充剂和抗菌伤口治疗，因此与人类接触高度相关。由于大量不同的纳米粒子已用于各种产品中并正在开发新应用，因此建立适合这些新材料的相关、快速且廉价的体外风险评估方法至关重要。因此，本研究使用简单的肝细胞模型结合体内注射模型来模拟暴露后（例如通过摄入或吸入）少量纳米颗粒进入血流，并检查了雌性Wistar大鼠通过静脉注射50克纳米颗粒进行体内暴露以及使用人肝细胞系进行体外暴露后，直径20纳米的银纳米颗粒在肝脏中引起毒性、炎症和氧化应激的可能性。 C3A。我们发现Ag NPs对肝细胞具有高度细胞毒性（LC50乳酸脱氢酶：2.5 g/cm(2)），并通过减少白蛋白释放影响肝细胞稳态。在具有正常细胞或组织形态的亚致死浓度下，在肝细胞的细胞质和细胞核中检测到Ag NP。我们在体外和体内观察到Ag NPs对炎症介质表达的类似影响，两种模型中白细胞介素8（IL-8）/巨噬细胞炎症蛋白2、IL-1RI和肿瘤坏死因子表达的增加以及体外IL-8蛋白释放的增加。本文提供了银纳米颗粒摄入后在肝脏中具有潜在毒性和致炎潜力的证据。此外，体外和体内反应之间的相似性是惊人的，并且对于未来通过在颗粒风险评估中使用肝细胞系来减少、完善和替代动物研究来说是令人鼓舞的。
With the increasing use and incorporation of nanoparticles (NPs) into consumer products, screening for potential toxicity is necessary to ensure customer safety. NPs have been shown to translocate to the bloodstream following inhalation and ingestion, and such studies demonstrate that the liver is an important organ for accumulation. Silver (Ag) NPs are highly relevant for human exposure due to their use in food contact materials, dietary supplements, and antibacterial wound treatments. Due to the large number of different NPs already used in various products and being developed for new applications, it is essential that relevant, quick, and cheap methods of in vitro risk assessment suitable for these new materials are established. Therefore, this study used a simple hepatocytes model combined with an in vivo injection model to simulate the passage of a small amount of NPs into the bloodstream following exposure, e.g., via ingestion or inhalation, and examined the potential of Ag NPs of 20nm diameter to cause toxicity, inflammation, and oxidative stress in the liver following in vivo exposures of female Wistar rats via iv injection to 50 g of NPs and in vitro exposures using the human hepatocyte cell line C3A. We found that Ag NPs were highly cytotoxic to hepatocytes (LC50 lactate dehydrogenase: 2.5 g/cm(2)) and affected hepatocyte homeostasis by reducing albumin release. At sublethal concentrations with normal cell or tissue morphology, Ag NPs were detected in cytoplasm and nuclei of hepatocytes. We observed similar effects of Ag NPs on inflammatory mediator expression in vitro and in vivo with increase of interleukin-8 (IL-8)/macrophage inflammatory protein 2, IL-1RI, and tumor necrosis factor- expression in both models and increased IL-8 protein release in vitro. This article presents evidence of the potential toxicity and inflammogenic potential of Ag NPs in the liver following ingestion. In addition, the similarities between in vitro and in vivo responses are striking and encouraging for future reduction, refinement, and replacement of animal studies by the use of hepatocyte cell lines in particle risk assessment.