Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family.
Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family.
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DOI：
10.1186/s12989-016-0145-5
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发表时间：
2016-06-21
影响因子：
10
通讯作者：
Erdely A
中科院分区：
文献类型：
--
作者：
Roberts JR;Mercer RR;Stefaniak AB;Seehra MS;Geddam UK;Chaudhuri IS;Kyrlidis A;Kodali VK;Sager T;Kenyon A;Bilgesu SA;Eye T;Scabilloni JF;Leonard SS;Fix NR;Schwegler-Berry D;Farris BY;Wolfarth MG;Porter DW;Castranova V;Erdely A
石墨烯是一种单层碳，是一种工程纳米材料（ENM），其物理和化学性质可以提供优于其他碳质ENM（如碳纳米管（CNT））的应用优势。本研究的目的是比较评估石墨纳米片（石墨烯基纳米材料家族的一员）在纳米片尺寸方面的肺和全身毒性。表征了厚度范围为8-25 nm的三种尺寸的石墨纳米片[20 μm横向（Gr 20）、5 μm横向（Gr 5）和<2 μm横向（Gr 1）]的表面积、结构、zeta电位和在分散介质（用于体内研究的载体）中的团聚的差异。通过咽部抽吸将小鼠暴露于这3种尺寸的石墨纳米片，剂量为4或40 μg/小鼠，或暴露于炭黑（CB）作为含碳对照材料。在暴露后4 h、1天、7天、1个月和2个月，进行支气管肺泡灌洗以收集液体和细胞用于分析肺损伤和炎症。评价肺组织中微粒清除率、组织病理学和基因表达。此外，测量血液、心脏、主动脉和肝脏中的蛋白质水平和基因表达，以评估全身反应。所有的Gr样品被发现是类似的两个石墨结构组成，并附聚到不同程度的DM成比例的横向尺寸。Gr 1的表面积比Gr 5和Gr 20大约7倍，但每平方米的反应活性较低。在低剂量下，Gr材料均未诱导毒性。在高剂量下，与Gr 1和CB相比，Gr 20和Gr 5暴露在更大程度和持续时间上增加了灌洗液和组织基因表达中的肺部炎症和损伤指数。暴露后2个月，Gr 5和Gr 20显示无或极轻微的肺上皮肥大和增生，且未发生纤维化。此外，相对于Gr 1，Gr 5和Gr 20中的主动脉和肝脏炎症和急性期基因短暂升高。石墨纳米片的肺和全身毒性可能取决于横向尺寸和/或表面反应性，其中相对于1-2 μm石墨纳米片，> 5 μm的石墨纳米片横向诱导更大的毒性，其在暴露后的早期时间点达到峰值。本文的在线版本（doi：10.1186/s12989-016-0145-5）包含补充材料，可供授权用户使用。
Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and <2 μm lateral (Gr1)] ranging from 8–25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m2. At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1–2 μm graphite nanoplate. The online version of this article (doi:10.1186/s12989-016-0145-5) contains supplementary material, which is available to authorized users.