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[聚乙烯吡咯烷酮稳定的胶体纳米银的毒理学评价。IV. 对肠道微生物群、免疫指标的影响]

[Toxicological evaluation of colloidal nano-sized silver stabilized polyvinylpyrrolidone. IV. Influence on intestinal microbiota, immune indexes].

作者信息

Shumakova A A, Shipelin V A, Efimochkina N R, Minaeva L P, Bykova I B, Markova Yu M, Trushina E N, Mustafina O K, Gmoshinsky I V, Khanferyan R A, Khotimchenko S A, Sheveleva S A, Tutelyan V A

机构信息

Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow.

出版信息

Vopr Pitan. 2016;85(3):27-35. doi: 10.24411/0042-8833-2016-00032. Epub 2016 Jun 23.

Abstract

Nano-sized colloidal silver (NCS) stabilized with polyvinylpyrrolidone (PVP) containing nanoparticles (NPs) of silver with a diameter of 10-80 nm was administered to growing male rats (body weight 80±10 g) during the first 30 days by intragastric gavage and then for 62 days with diet consumed in doses of 0.1, 1.0 and 10 mg/kg of body weight per day based on silver (Ag). The control animals received deionized water and PVP. The composition of microbiota from the cecum was studied using standard microbiological methods with determination of the main and transient components, together with antagonistic activity of symbiotic bifidobacteria. Expression of antigens CD45RA, CD3, CD4, CD8, CD161a on lymphocytes (Ly) of peripheral blood was determined by flow cytometry; blood serum levels of cytokines IL10, IL13, TNFα were examined by ELISA. It was shown that subacute administration of colloidal Ag in all studied doses did not lead to significant changes in the composition of the main components of normal microbiota, providing, however, the inhibitory effect on the growth of some transitory components probably including opportunistic species of microorganisms. Among the studied immunological parameters decreased amount of B-Ly was noticed at the highest dose of the NCS, while changes in the other parameters of the immune system were depended ambiguously on the dose of the product. The results were analyzed in conjunction with the data of previous publications concerning the impact on the NCS on integrated, morphological, hematological, biochemical and enzymological indexes of animals in the 92-day experiment. It was concluded that significant symptoms of NCS sub-acute oral toxicity manifested starting from a dose of 1 mg/kg body weight of Ag, and the maximum not observed adverse effect dose (NOAEL) can be estimated as 0.1 mg/kg body weight.

摘要

用聚乙烯吡咯烷酮(PVP)稳定的纳米级胶体银(NCS),其含有的银纳米颗粒(NPs)直径为10 - 80纳米,在最初30天通过灌胃给予生长中的雄性大鼠(体重80±10克),然后在接下来的62天通过饮食给予,剂量分别为每天0.1、1.0和10毫克银(Ag)/千克体重。对照动物接受去离子水和PVP。使用标准微生物学方法研究盲肠微生物群的组成,测定主要和短暂成分,以及共生双歧杆菌的拮抗活性。通过流式细胞术测定外周血淋巴细胞(Ly)上抗原CD45RA、CD3、CD4、CD8、CD161a的表达;通过酶联免疫吸附测定法检测血清细胞因子IL10、IL13、TNFα的水平。结果表明,所有研究剂量的胶体银亚急性给药均未导致正常微生物群主要成分的组成发生显著变化,但对一些可能包括机会性微生物种类的短暂成分的生长具有抑制作用。在研究的免疫参数中,在最高剂量的NCS下观察到B淋巴细胞数量减少,而免疫系统的其他参数变化与产品剂量的关系不明确。结合先前关于92天实验中NCS对动物综合、形态、血液学、生化和酶学指标影响的出版物数据对结果进行了分析。得出的结论是,从1毫克银/千克体重的剂量开始出现NCS亚急性口服毒性的显著症状,最大未观察到有害作用剂量(NOAEL)可估计为0.1毫克银/千克体重。

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