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[用聚乙烯吡咯烷酮稳定的纳米级胶体银的毒理学评价。I.纳米材料的表征、整体、血液学参数、硫醇化合物水平和肝细胞凋亡]

[Toxicological evaluation of nanosized colloidal silver, stabilized with polyvinylpyrrolidone. I. Characterization of nanomaterial, integral, hematological parameters, level of thiol compounds and liver cell apoptosis].

作者信息

Shumakova A A, Shipelin V A, Sidorova Yu S, Trushina E N, Mustafina O K, Pridvorova S M, Gmoshinsky I V, Khotimchenko S A

出版信息

Vopr Pitan. 2015;84(6):46-57.

Abstract

Nano-sized colloidal silver (NCS) is currently one of the most widely used nanomaterials in medicine and consumer’s products. Nanoparticles (NPs) of silver, in addition to the direct exposition through products may expose human via various environmental objects. The aim of the study is to assess the safe doses of silver NP received orally. The investigated NCS contained silver NPs with diameter of 10–60 nm, predominantly with a nearly spherical form stabilized with polyvinylpyrrolidone (PVP). The experiment was performed during 92 days in 5 groups of male Wistar rats (n=15 in each group), receiving a balanced semisynthetic diet. Animal of group 1 (control) received vehicle (deionized water) intragastrically for 30 days and then with food, groups from 2nd to 4th – PVP and groups from 3rd to 5th NCS, in doses respectively, 0.1; 1.0 and 10 mg/kg body weight (b.w.) in terms of silver. The dose of PVP in groups from 2nd to 5th did not differ, amounting to 200 mg/kg b.w. During the experiment, the weight gain, skin condition, activity, stool, cognitive function were assessed. At the end of the feeding period weight of internal organs, intestinal wall permeability to protein macromolecules, liver thiols, standard values of blood erythrocytes, leukocytes and platelets, hepatocyte apoptosis by flow cytometry were studied. These results suggest that in terms of weight gain, lung relative mass, average erythrocyte volume, hemoglobin content and concentration in erythrocytes, the relative proportion of lymphocytes and neutrophils adverse changes have been observed at a dose of 10 mg NPs per kg of b.w. At lower levels of exposure (0.1 and 1.0 mg/kg b.w.) some specific changes were also observed (in terms of thiols pool in liver, cognitive function, relative abundance of monocytes, the number of dead hepatocytes), which, however, did not possess an unambiguous dependence on the dose. Possible mechanisms of the toxic action of the NCS have been discussed.

摘要

纳米级胶体银(NCS)是目前医学和消费品中使用最广泛的纳米材料之一。银纳米颗粒(NPs)除了通过产品直接接触外,还可能通过各种环境物体使人类接触到。本研究的目的是评估口服银纳米颗粒的安全剂量。所研究的NCS包含直径为10 - 60nm的银纳米颗粒,主要呈近似球形,由聚乙烯吡咯烷酮(PVP)稳定。实验在92天内对5组雄性Wistar大鼠(每组n = 15)进行,给予均衡的半合成饮食。第1组(对照组)动物经胃内给予赋形剂(去离子水)30天,然后与食物一起给予,第2组至第4组给予PVP,第3组至第5组给予NCS,银的剂量分别为0.1、1.0和每千克体重(b.w.)10mg。第2组至第5组中PVP的剂量没有差异,为每千克体重200mg。在实验过程中,评估了体重增加、皮肤状况、活动、粪便、认知功能。在喂养期结束时,研究了内脏重量、肠壁对蛋白质大分子的通透性、肝脏硫醇、血液红细胞、白细胞和血小板的标准值、通过流式细胞术检测的肝细胞凋亡。这些结果表明,就体重增加、肺相对质量、平均红细胞体积、血红蛋白含量和红细胞浓度而言,在每千克体重10mg纳米颗粒的剂量下观察到淋巴细胞和中性粒细胞的相对比例出现了不利变化。在较低暴露水平(每千克体重0.1和1.0mg)下也观察到了一些特定变化(就肝脏中的硫醇池、认知功能、单核细胞的相对丰度、死亡肝细胞的数量而言),然而,这些变化与剂量并没有明确的依赖性。已讨论了NCS毒性作用的可能机制。

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