Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes.

Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes.
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DOI:
10.1186/1743-8977-9-38
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发表时间:
2012-10-16
影响因子:
10
通讯作者:
Wingard CJ
Wingard CJ
中科院分区:
医学1区
文献类型:
--
作者:
Urankar RN;Lust RM;Mann E;Katwa P;Wang X;Podila R;Hilderbrand SC;Harrison BS;Chen P;Ke PC;Rao AM;Brown JM;Wingard CJ

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碳纳米管卓越的物理化学性质使其在多种商业和生物医学应用中得到应用。然而,它们的使用引起了人们对人类接触可能使个人易受不利健康风险的关注。本研究探讨了心脏缺血性损伤的易感性,单次暴露于各种形式的多壁碳纳米管(MWCNTs)。假设多壁碳纳米管的口咽吸入加重心肌缺血和再灌注损伤(I/R损伤)。对雄性C57 BL/6 J小鼠进行口咽抽吸,将单次量的MWCNT(0.01 - 100 μg)悬浮在100 μL表面活性剂盐水(SS)溶液中。三种形式的多壁碳纳米管在这项研究中使用:未改性的,商业级(C级),和官能化的形式,通过酸处理(羧化,COOH)或氮化(N-掺杂)和SS车辆进行修改。在抽吸后1、7和28天评估肺炎症、血清细胞因子谱和心脏缺血/再灌注(I/R)损伤。通过支气管肺泡灌洗液(BALF)评估的MWCNT口咽抽吸的肺反应显示蛋白质和炎性细胞募集适度增加。与SS组相比,肺组织学显示中度组织炎症。暴露后1天,吸入羧基化MWCNT的小鼠中嗜酸性粒细胞趋化因子的血清水平显着升高。口咽抽吸所有三种形式的多壁碳纳米管导致心肌梗死的时间和/或剂量依赖性恶化。心肌损伤的严重程度因所用MWCNTs的形式而异。N-掺杂的MWCNT在任何时间点产生最大的梗塞扩展,并且需要较低的对数浓度来建立无作用水平。吸入COOH和N掺杂形式后28天,I/R损伤的扩展仍然显著升高,但与SS相比,C级损伤没有显著升高。我们的研究结果表明,口咽部吸入多壁碳纳米管促进心脏组织缺血/再灌注损伤的易感性增加,而没有显着的肺部炎症反应。在低浓度的多壁碳纳米管下观察到心脏损伤效应,多壁碳纳米管的存在可能对心血管系统构成重大风险。
The exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs). It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury). Oropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg) suspended in 100 μL of a surfactant saline (SS) solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade), and functionalized forms that were modified either by acid treatment (carboxylated, COOH) or nitrogenation (N-doped) and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R) injury were assessed at 1, 7 and 28 days post-aspiration. Pulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF) revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but not the C-grade as compared to SS. Our results suggest that oropharyngeal aspiration of MWCNT promotes increased susceptibility of cardiac tissue to ischemia/reperfusion injury without a significant pulmonary inflammatory response. The cardiac injury effects were observed at low concentrations of MWCNTs and presence of MWCNTs may pose a significant risk to the cardiovascular system.
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