The pulmonary toxicity of carboxylated or aminated multi-walled carbon nanotubes in mice is determined by the prior purification method.

The pulmonary toxicity of carboxylated or aminated multi-walled carbon nanotubes in mice is determined by the prior purification method.
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DOI:
10.1186/s12989-020-00390-y
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发表时间:
2020-11-26
影响因子:
10
通讯作者:
Bonner JC
Bonner JC
中科院分区:
医学1区
文献类型:
--
作者:
Taylor-Just AJ;Ihrie MD;Duke KS;Lee HY;You DJ;Hussain S;Kodali VK;Ziemann C;Creutzenberg O;Vulpoi A;Turcu F;Potara M;Todea M;van den Brule S;Lison D;Bonner JC

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吸入多壁碳纳米管(MWCNT)对人类健康构成潜在风险。为了保护工人和消费者的安全,需要确定多壁碳纳米管的毒性。功能化已被证明可以减少或增加与多壁碳纳米管相关的肺损伤,具体取决于修饰的类型。因此,我们研究了源自常见原始母体化合物 (NC7000) 的多壁碳纳米管库的急性和慢性肺毒性。多壁碳纳米管经过热或化学纯化,随后通过羧化或胺化进行表面功能化。为了评估肺毒性,通过口咽抽吸给雄性C57BL6小鼠施用1.6或4mg/kg的每种MWCNT类型。 Mitsui-7 MWCNT用作阳性对照。暴露后第 3 天和第 60 天进行尸检,收集支气管肺泡灌洗液 (BALF) 和肺部。第 3 天,所有 MWCNT 均增加了 BALF 中的中性粒细胞数量。化学纯化对BALF中促炎细胞因子(IL-1β、IL-6、CXCL1)影响较大,而热纯化对促纤维化细胞因子(CCL2、OPN、TGF-β1)影响较大。第 60 天时,热纯化的羧化 MWCNT 对 BALF 中淋巴细胞数量的影响最强。热纯化的 MWCNT 导致 BALF 中 LDH 和总蛋白的最大增加。此外,热纯化和羧基或胺功能化的多壁碳纳米管在肺部引起最多数量的肉芽肿性病变。拉曼光谱表明,与热纯化衍生物毒性增加相关的物理化学特征主要是表面缺陷减少和无定形含量减少。这些数据表明,纯化方法是羧基和胺功能化多壁碳纳米管引起的肺毒性的重要决定因素。在线版本包含可在 10.1186/s12989-020-00390-y 获取的补充材料。
Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs. The online version contains supplementary material available at 10.1186/s12989-020-00390-y.
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