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单次口服给予后大鼠体内纳米银颗粒和银离子的毒代动力学差异及其毒性

Toxicokinetic differences and toxicities of silver nanoparticles and silver ions in rats after single oral administration.

机构信息

a College of Pharmacy, Dongduk Women's University , Seoul , Korea.

出版信息

J Toxicol Environ Health A. 2013;76(22):1246-60. doi: 10.1080/15287394.2013.849635.

Abstract

Blood levels, tissue distributions, and excretion of silver (Ag) were measured in male Sprague-Dawley rats (n = 5) up to 24 h after a single oral administration of silver nanoparticles (AgNP) and silver ions (Ag(+)), respectively. The AUC24hr of Ag(+) was 3.81 ± 0.57 μg/d/ml when rats were treated with a single dose of 20 mg/kg, whereas that of AgNP was 1.58 ± 0.25 μg/d/ml. Tissue distribution of Ag in liver, kidneys, and lungs was higher when Ag(+) was administered compared to AgNP. Orally administered AgNP were predominantly excreted through feces, suggesting low bioavailability. Death or body weight changes were not observed in the Ag(+)- or AgNP-treated groups. However, decreased red blood cell counts, hematocrit, and hemoglobin were found in the Ag(+)-treated groups, while increased platelet counts and mean platelet volume were noted in the AgNP-treated rats. A serum biochemical analysis showed that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) rose significantly following Ag(+) treatment (20 mg/kg). AgNP treatment (2 or 20 mg/kg) also elevated AST, whereas infiltration of mononuclear cells with liver necrosis was found only in the 20 mg/kg Ag(+)-treated animals.

摘要

在单次口服给予银纳米粒子(AgNP)和银离子(Ag(+))后,雄性 Sprague-Dawley 大鼠(n=5)在 24 小时内测量了血液水平、组织分布和排泄的银含量。当大鼠以 20mg/kg 的单剂量接受治疗时,Ag(+)的 AUC24hr 为 3.81±0.57μg/d/ml,而 AgNP 的 AUC24hr 为 1.58±0.25μg/d/ml。与 AgNP 相比,给予 Ag(+)时肝脏、肾脏和肺部的 Ag 组织分布更高。口服给予的 AgNP 主要通过粪便排泄,表明生物利用度低。在 Ag(+)或 AgNP 处理组中未观察到死亡或体重变化。然而,在 Ag(+)处理组中发现红细胞计数、血细胞比容和血红蛋白减少,而在 AgNP 处理的大鼠中发现血小板计数和平均血小板体积增加。血清生化分析显示,AST 和 ALT 在 Ag(+)处理(20mg/kg)后显著升高。AgNP 处理(2 或 20mg/kg)也升高了 AST,而只有在 20mg/kg Ag(+)处理的动物中才发现单核细胞浸润和肝坏死。

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