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大鼠腹腔内给予单链 DNA 功能化多壁碳纳米管后短暂的氧化应激和炎症反应。

Transient oxidative stress and inflammation after intraperitoneal administration of multiwalled carbon nanotubes functionalized with single strand DNA in rats.

机构信息

Department of Physiology, University of Medicine and Pharmacy, Cluj-Napoca, Romania.

出版信息

Toxicol Appl Pharmacol. 2012 Mar 15;259(3):281-92. doi: 10.1016/j.taap.2012.01.004. Epub 2012 Jan 16.

Abstract

Multi-walled carbon nanotubes (MWCNTs) are widely used for nanotechnology. Their impact on living organisms is, however, not entirely clarified. Oxidative stress and inflammation seem to be the key mechanisms involved in MWCNTs' cytotoxicity. Until present, pulmonary and skin models were the main tested experimental designs to assess carbon nanotubes' toxicity. The systemic administration of MWCNTs is essential, with respect for future medical applications. Our research is performed on Wistar rats and is focused on the dynamics of oxidative stress parameters in blood and liver and pro-inflammatory cytokines in liver, after single dose (270mgl(-1)) ip administration of MWCNTs (exterior diameter 15-25nm, interior diameter 10-15nm, surface 88m(2)g(-1)) functionalized with single strand DNA (ss-DNA). The presence of MWCNTs in blood was assessed by Raman spectroscopy, while in liver histological examination and confocal microscopy were used. It was found that ss-DNA-MWCNTs induce oxidative stress in plasma and liver, with the return of the tested parameters to normal values, 6h after ip injection of nanotubes, with the exception of reduced glutathione in plasma. The inflammatory cytokines (TNF-α, IL-1β) had a similar pattern of evolution. We also assessed the level of ERK1/2 and the phosphorylation of p65 subunit of NF-kB in liver that had a transient increase and returned to normal at the end of the tested period. Our results demonstrate that ss-DNA-MWCNTs produce oxidative stress and inflammation, but with a transient pattern. Given the fact that antioxidants modify the profile not only for oxidative stress, but also of inflammation, the dynamics of these alterations may be of practical importance for future protective strategies.

摘要

多壁碳纳米管 (MWCNTs) 被广泛应用于纳米技术。然而,它们对生物体的影响尚未完全阐明。氧化应激和炎症似乎是 MWCNTs 细胞毒性的关键机制。迄今为止,肺部和皮肤模型是评估碳纳米管毒性的主要实验设计。考虑到未来的医学应用,MWCNTs 的全身给药是必不可少的。我们的研究对象是 Wistar 大鼠,研究重点是单次腹腔注射 (270mgl(-1)) 多壁碳纳米管 (外径 15-25nm,内径 10-15nm,表面 88m(2)g(-1)) 后血液和肝脏中氧化应激参数的动力学以及肝脏中促炎细胞因子的动力学。这些多壁碳纳米管经单链 DNA (ss-DNA) 功能化。通过拉曼光谱评估血液中 MWCNTs 的存在,而在肝脏中则进行组织学检查和共聚焦显微镜检查。结果发现,ss-DNA-MWCNTs 诱导血浆和肝脏氧化应激,在腹腔注射纳米管 6 小时后,除了血浆中的还原型谷胱甘肽外,所有测试参数均恢复正常。炎症细胞因子 (TNF-α、IL-1β) 的变化模式相似。我们还评估了肝脏中 ERK1/2 和 NF-κB p65 亚基磷酸化的水平,它们有短暂的增加,并在测试结束时恢复正常。我们的研究结果表明,ss-DNA-MWCNTs 会产生氧化应激和炎症,但呈短暂模式。鉴于抗氧化剂不仅可以改变氧化应激的模式,还可以改变炎症的模式,因此这些变化的动态可能对未来的保护策略具有实际意义。

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