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评价 NiO 纳米粒子在体内和体外引起的急性氧化应激。

Evaluation of acute oxidative stress induced by NiO nanoparticles in vivo and in vitro.

机构信息

Health Research Institute, Ikeda, Osaka, Japan.

出版信息

J Occup Health. 2011;53(2):64-74. doi: 10.1539/joh.l10121. Epub 2011 Jan 11.

Abstract

OBJECTIVES

Nickel oxide (NiO) is an important industrial material, and it is also a harmful agent. The toxicity of NiO is size-related: nanoparticles are more toxic than fine-particles. The toxic mechanism induced by NiO nanoparticles remains unexplained, and the relationship between in vitro and in vivo NiO toxicity results is unclear. In the present study, we focused on the oxidative stress caused by NiO nanoparticles by examining and comparing in vitro and in vivo acute responses induced by NiO nanoparticles.

METHODS

Cellular responses induced by black NiO nanoparticles with a primary particle size of 20 nm, were examined in human lung carcinoma A549 cells. In vivo responses were examined by instillation of NiO nanoparticles into rat trachea. Bronchoalveolar lavage fluid (BALF) was collected after intratracheal instillation at different time points, and concentrations of lipid peroxide heme oxygenase-1 (HO-1), surfactant protein-D (SP-D) and lactate dehydrogenase (LDH) in BALF were measured.

RESULTS

The levels of intracellular reactive oxygen species and lipid peroxidation in A549 cells increased with increasing exposure to NiO nanoparticles, and increases in gene expressions of HO-1 and SP-D were observed in A549 cells. The lipid peroxide level in BALF significantly increased after 24 h instillation but decreased three days later. LDH leakage was also observed three days later.

CONCLUSIONS

NiO nanoparticles induce oxidative stress-related lung injury. In vivo and in vitro oxidative stress was induced resulting in activation of antioxidant systems. Based on these responses, we conclude that the results of the in vivo and in vitro studies tend to correspond.

摘要

目的

氧化镍(NiO)是一种重要的工业材料,也是一种有害剂。NiO 的毒性与其粒径有关:纳米颗粒比细颗粒毒性更大。NiO 纳米颗粒诱导的毒性机制尚不清楚,体外和体内 NiO 毒性结果之间的关系也不清楚。在本研究中,我们通过检查和比较 NiO 纳米颗粒体外和体内急性反应,重点研究了 NiO 纳米颗粒引起的氧化应激。

方法

用粒径为 20nm 的黑色 NiO 纳米颗粒作用于人肺癌 A549 细胞,检测细胞反应。通过将 NiO 纳米颗粒注入大鼠气管来检测体内反应。气管内滴注后不同时间点收集支气管肺泡灌洗液(BALF),并测定 BALF 中脂质过氧化物血红素加氧酶-1(HO-1)、表面活性蛋白-D(SP-D)和乳酸脱氢酶(LDH)的浓度。

结果

A549 细胞内活性氧和脂质过氧化水平随 NiO 纳米颗粒暴露量的增加而增加,A549 细胞中 HO-1 和 SP-D 的基因表达也增加。滴注 24 小时后 BALF 中的脂质过氧化物水平显著升高,但三天后降低。三天后还观察到 LDH 泄漏。

结论

NiO 纳米颗粒诱导与氧化应激相关的肺损伤。体内和体外氧化应激导致抗氧化系统激活。基于这些反应,我们得出结论,体内和体外研究的结果趋于一致。

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