Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles

Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles
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DOI:
10.3109/15376516.2013.780196
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发表时间:
2013-07-01
影响因子:
3.2
通讯作者:
Yu, Il Je
Yu, Il Je
中科院分区:
医学4区
文献类型:
--
作者:
Dong, Mi Sook;Choi, Ji-Yoon;Yu, Il Je

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银纳米粒子(AgNP)的特殊性质,例如抗菌活性和导电性,使其能够应用于许多领域。然而,它们的不断扩大的应用也引发了健康、环境和安全方面的担忧。先前的体内 AgNP 毒性研究表明,肾脏中银的积累存在性别差异,女性肾脏中的银含量是男性肾脏的 2-3 倍。然而,没有其他研究进一步解决这种性别差异。因此,本研究基于对通过吸入 AgNP 12 周的大鼠肾脏进行的毒理学研究,调查了 AgNP 对肾脏基因水平的性别依赖性影响。与新鲜空气对照相比,暴露于银纳米颗粒的肾脏包含 104 个基因,表达量增加了 1.3 倍以上。对于暴露于低剂量或高剂量纳米银的雄性大鼠肾脏,96个基因表现出表达变化,其中6个基因随着低剂量和高剂量而变化;四个增加,两个减少。同时,暴露于低剂量或高剂量纳米银的雌性大鼠肾脏中,66个基因出现表达变化,其中11个基因随低剂量和高剂量均发生变化;九个增加,两个减少。超过2倍的性别依赖性基因表达变化与163个基因相关,其中男性肾脏中有79个基因,女性肾脏中有84个基因,加上超过5倍的性别依赖性基因表达变化与21个基因相关。然而,12 周的银纳米颗粒吸入​​暴露并没有激活涉及细胞凋亡或细胞周期的基因。总体而言,雄性大鼠肾脏表现出较高的参与外源代谢的基因表达,而雌性大鼠肾脏表现出较高的参与细胞外信号传导的基因表达。
The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous in vivo AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.