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[聚乙烯吡咯烷酮稳定的纳米胶体银在大鼠92天实验中的毒理学评价。II. 内脏器官形态学]

[Toxicological evaluation of nanosized colloidal silver, stabilized with polyvinylpyrrolidone, in 92-day experiment on rats. II. Internal organs morphology].

作者信息

Zaytseva N V, Zemlyanova M A, Zvezdin V N, Dovbysh A A, Gmoshinsky I V, Khotimchenko S A, Akafieva T I

出版信息

Vopr Pitan. 2016;85(1):47-55.

PMID:27228701
Abstract

The aim of the study was to evaluate the safe doses of commercially available nanosized colloidal silver (NCS), stabilized with polyvinilpirrolidone (PVP, food additive E1201) when administered in gastrointestinal tract of rats in the 92-day experiment in terms of the morphological changes in the internals of animals. The sample studied contained non-aggregated nanoparticles (NPs) of silver belonging to size fractions with a diameter of less than 5 nm, 10-20 nm or 50-80 nm. 80% of NPs were inside the range of hydrodynamic diameters 10.6-61.8 nm. The preparation of NCS was administered to growing male Wistar rats. (initial body weight 80 ± 10 g) for 1 month by intragastric gavage and then consumed with food at doses of 0.1, 1.0 and 10 mg/kg of body weight based on silver. The control animals received water or vehicle of nanomaterial--water solution of PVP. After withdrawal of animals from the experiment by exsanguination under ether anesthesia organs (liver, spleen, kidney, ileum) were isolated and their slides were prepared by standard methods following 'by staining with hematoxylin-eosin. Analysis was performed in light optical microscope equipped with a digital camera at a magnification from 1 x 100 to 1 x 1000. It was shown that the experimental animals treated with the NCS developed series of morphological changes in the tissues of the internal organs (liver, spleen and kidney) with the elevation of the range and severity of structural changes with increasing doses of silver. The most sensitive target of NCS action was apparently liver, which has already shown at a dose of 0.1 mg of silver NP/kg of body weight marked eosinophilic infiltration of portal tracts, which was accompanied at doses of 1.0 and 10.0 mg/kg by the emergence of medium and large-drop fat vacuoles in the cytoplasm of hepatocytes, swelling and lympho-macrophage. infiltration of the portal tracts. Detectable changes can be regarded as symptoms of inflammation of hepatocytes, at least, at a dose nanomaterial of 1.0 mg/kg body weight or more. Relative intensity of morphological changes in the internal organs correlated with published data on the biodistribution of silver NP administered to the gastrointestinal tract. It is concluded that the threshold dose corresponding to the minimum adverse effect of NCS is, according to the study of the above, no more than 1.0 mg/kg of body weight based on silver.

摘要

本研究的目的是在为期92天的实验中,通过观察大鼠胃肠道内给予用聚乙烯吡咯烷酮(PVP,食品添加剂E1201)稳定的市售纳米级胶体银(NCS)后动物内脏的形态变化,来评估其安全剂量。所研究的样品包含直径小于5nm、10 - 20nm或50 - 80nm尺寸级分的非聚集银纳米颗粒(NP)。80%的NP流体动力学直径在10.6 - 61.8nm范围内。将NCS制剂经胃内灌胃给予生长中的雄性Wistar大鼠(初始体重80±10g)1个月,然后以基于银的0.1、1.0和10mg/kg体重的剂量与食物一起摄入。对照动物接受水或纳米材料的赋形剂——PVP水溶液。在乙醚麻醉下通过放血使动物退出实验后,分离出器官(肝脏、脾脏、肾脏、回肠),并按照苏木精 - 伊红染色的标准方法制备其切片。在配备数码相机的光学显微镜下以1×100至1×1000的放大倍数进行分析。结果表明,用NCS处理的实验动物内脏器官(肝脏、脾脏和肾脏)组织出现了一系列形态变化,随着银剂量的增加,结构变化的范围和严重程度也增加。NCS作用最敏感的靶器官显然是肝脏,在银NP剂量为0.1mg/kg体重时就已出现门静脉嗜酸性粒细胞浸润,在剂量为1.0和10.0mg/kg时,肝细胞胞质中出现中、大滴脂肪空泡,门静脉肿胀以及淋巴细胞 - 巨噬细胞浸润。至少在纳米材料剂量为1.0mg/kg体重及以上时,可检测到的变化可视为肝细胞炎症的症状。内脏器官形态变化的相对强度与已发表的关于胃肠道给予银NP的生物分布数据相关。根据上述研究得出结论,对应于NCS最小不良反应的阈值剂量按银计算不超过1.0mg/kg体重。

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