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亚急性暴露于二氧化钛、氧化锌和氧化铝纳米颗粒对小鼠肝脏和大脑氧化应激及组织学变化的影响

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.

作者信息

Shrivastava Rupal, Raza Saimah, Yadav Abhishek, Kushwaha Pramod, Flora Swaran J S

机构信息

Division of Regulatory Toxicology, Defence Research and Development Establishment , Gwalior , India.

出版信息

Drug Chem Toxicol. 2014 Jul;37(3):336-47. doi: 10.3109/01480545.2013.866134. Epub 2013 Dec 17.

Abstract

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

摘要

纳米材料处于快速发展的纳米技术领域的前沿。然而,关于这些纳米颗粒对人类和环境毒性的信息仍然不足。本研究调查了三种金属氧化物纳米颗粒二氧化钛(TiO₂)、氧化锌(ZnO)和氧化铝(Al₂O₃)对小鼠红细胞、脑和肝脏的毒性作用。雄性小鼠连续21天每天口服单剂量500毫克/千克的每种纳米颗粒。结果表明,暴露于这些纳米金属颗粒会在红细胞、肝脏和大脑中产生显著的氧化应激,这从活性氧(ROS)水平升高和抗氧化酶活性改变中明显可见。大脑皮质中多巴胺和去甲肾上腺素水平显著升高以及大脑氧化应激增加表明这些纳米颗粒具有神经毒性潜力。透射电子显微镜(TEM)分析表明这些纳米颗粒存在于细胞质和细胞核内。这些变化也得到了铜锌超氧化物歧化酶(CuZnSOD)和锰超氧化物歧化酶(MnSOD)抑制的支持,这两种酶被认为是氧化应激的重要生物标志物。这些纳米颗粒产生的毒性作用在氧化锌的情况下更为明显,其次分别是氧化铝和二氧化钛。目前的结果进一步表明氧化应激是纳米颗粒诱导毒性表现所涉及的主要机制之一。

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