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功能化单壁碳纳米管的急性毒性:一种生物化学、组织病理学和蛋白质组学方法。

Acute toxicity of functionalized single wall carbon nanotubes: A biochemical, histopathologic and proteomics approach.

作者信息

Ahmadi Homa, Ramezani Mohammad, Yazdian-Robati Rezvan, Behnam Behzad, Razavi Azarkhiavi Kamal, Hashem Nia Azadeh, Mokhtarzadeh Ahad, Matbou Riahi Maryam, Razavi Bibi Marjan, Abnous Khalil

机构信息

Department od Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Chem Biol Interact. 2017 Sep 25;275:196-209. doi: 10.1016/j.cbi.2017.08.004. Epub 2017 Aug 12.

DOI:10.1016/j.cbi.2017.08.004
PMID:28807745
Abstract

Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice). One or 7 days after intravenous injection, the mice were killed and serum and livers were collected. The oxidative stress markers, biochemical and histopathological changes were studied. Subsequently, proteomics approach was used to investigate the alterations of protein expression profiles in the liver. Results showed that there were not any significant differences in malondealdehyde (MDA), glutathione (GSH) levels and biochemical enzymes (ALT and AST) between groups, while the histopathological observations of livers showed some injuries. The results of proteomics analysis revealed indolethylamine N-Methyltransferase (INMT), glycine N-Methyltransferase (GNMT), selenium binding protein (Selenbp), thioredoxin peroxidase (TPx), TNF receptor associated protein 1(Trap1), peroxiredoxin-6 (Prdx6), electron transport flavoprotein (Etf-α), regucalcin (Rgn) and ATP5b proteins were differentially expressed in functionalized SWCNTs groups. Western blot analyses confirmed that the changes in Prdx6 were consistent with 2-DE gel analysis. In summary, acute toxicological study on two functionalized SWCNTs did not show any significant toxicity at selected doses. Proteomics analysis also showed that following exposure to functionalized SWCNTs, the expression of some proteins with antioxidant activity and detoxifying properties were increased in liver tissue.

摘要

最近,碳纳米管(CNTs)在不同的生物医学应用中显示出了有前景的潜力,但其在人体中的安全使用以及可能存在的毒性仍然具有挑战性。本研究的目的是确定功能化单壁碳纳米管(SWCNTs)的急性毒性。在这个项目中,制备了聚乙二醇化和吐温功能化的SWCNTs。将BALB/c小鼠随机分为九组,包括聚乙二醇化SWCNTs(75、150μg/小鼠)和聚乙二醇、吐温80悬浮的SWCNTs、吐温80以及一个对照组(未处理小鼠)。静脉注射1天或7天后,处死小鼠并收集血清和肝脏。研究了氧化应激标志物、生化和组织病理学变化。随后,采用蛋白质组学方法研究肝脏中蛋白质表达谱的改变。结果表明,各组之间丙二醛(MDA)、谷胱甘肽(GSH)水平和生化酶(ALT和AST)没有任何显著差异,而肝脏的组织病理学观察显示有一些损伤。蛋白质组学分析结果显示,吲哚乙胺N-甲基转移酶(INMT)、甘氨酸N-甲基转移酶(GNMT)、硒结合蛋白(Selenbp)、硫氧还蛋白过氧化物酶(TPx)、肿瘤坏死因子受体相关蛋白1(Trap1)、过氧化物酶体增殖物激活受体6(Prdx6)、电子传递黄素蛋白(Etf-α)、钙网蛋白(Rgn)和ATP5b蛋白在功能化SWCNTs组中差异表达。蛋白质免疫印迹分析证实,Prdx6的变化与二维凝胶分析一致。总之,对两种功能化SWCNTs的急性毒理学研究在选定剂量下未显示出任何显著毒性。蛋白质组学分析还表明,暴露于功能化SWCNTs后,肝脏组织中一些具有抗氧化活性和解毒特性的蛋白质表达增加。

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