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氧化锌纳米颗粒通过活性氧诱导肾脏毒性。

Zinc oxide nanoparticles induce renal toxicity through reactive oxygen species.

作者信息

Xiao Lu, Liu Chunhua, Chen Xiaoniao, Yang Zhuo

机构信息

Medical School, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.

Medical School, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin 300071, China.

出版信息

Food Chem Toxicol. 2016 Apr;90:76-83. doi: 10.1016/j.fct.2016.02.002. Epub 2016 Feb 6.

DOI:10.1016/j.fct.2016.02.002
PMID:26860595
Abstract

Nanoparticles of zinc oxide (ZnO NPs) are applied in many fields nowadays. Consequently, concerns have been raised about its potential harmful effects. The present study focuses on its toxic effect on podocytes and rats. In vitro study, podocytes were treated with different concentrations of ZnO NPs (10, 50 and 100 μg/ml), the viability of cells was decreased as time prolonged according to MTT assay. Meantime, flow cytometry analysis indicated that ZnO NPs induced intracellular accumulation of reactive oxygen species (ROS) and apoptosis. The measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) showed that ZnO NPs decreased SOD level and increased MDA level. Interestingly, pretreatment with N-mercaptopropionyl-glycine, known as a type of ROS scavenger, could inhibit podocyte apoptosis induced by ZnO NPs. Meantime, a loss of nephrin can be detected, which may result in a direct damage to slit diaphragms. In vivo study, adult male Wistar rats were administrated with 3mg/kg/day ZnO NPs for 5 days, body weight and kidney index were significantly reduced. In addition, ZnO NPs decreased the activity of catalase and SOD in kidney cortex in vivo. It could be concluded that ZnO NPs present toxic effect on podocytes and Wistar rats, which was related with oxidative stress.

摘要

如今,氧化锌纳米颗粒(ZnO NPs)被应用于许多领域。因此,人们对其潜在的有害影响表示担忧。本研究聚焦于其对足细胞和大鼠的毒性作用。在体外研究中,用不同浓度的ZnO NPs(10、50和100μg/ml)处理足细胞,根据MTT试验,随着时间延长细胞活力降低。同时,流式细胞术分析表明ZnO NPs诱导细胞内活性氧(ROS)积累和细胞凋亡。超氧化物歧化酶(SOD)和丙二醛(MDA)的测定表明,ZnO NPs降低了SOD水平并提高了MDA水平。有趣的是,用N-巯基丙酰甘氨酸(一种ROS清除剂)预处理可抑制ZnO NPs诱导的足细胞凋亡。同时,可检测到nephrin的丢失,这可能导致裂孔隔膜的直接损伤。在体内研究中,成年雄性Wistar大鼠每天给予3mg/kg的ZnO NPs,持续5天,体重和肾脏指数显著降低。此外,ZnO NPs在体内降低了肾皮质中过氧化氢酶和SOD的活性。可以得出结论,ZnO NPs对足细胞和Wistar大鼠具有毒性作用,这与氧化应激有关。

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