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重复经口暴露后银纳米粒子的潜在肾毒性及其作用机制。

The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms.

机构信息

Department of Anatomical Sciences, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

BMC Nephrol. 2021 Jun 18;22(1):228. doi: 10.1186/s12882-021-02428-5.

DOI:10.1186/s12882-021-02428-5
PMID:34144690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8212496/
Abstract

BACKGROUND

Silver nanoparticles (AgNPs) can accumulate in various organs after oral exposure. The main objective of the current study is to evaluate the renal toxicity induced by AgNPs after repeated oral exposure and to determine the relevant molecular mechanisms.

METHODS

In this study, 40 male Wistar rats were treated with solutions containing 30, 125, 300, and 700 mg/kg of AgNPs. After 28 days of exposure, histopathological changes were assessed using hematoxylin-eosin (H&E), Masson's trichrome, and periodic acid-Schiff (PAS) staining. Apoptosis was quantified by TUNEL and immunohistochemistry of caspase-3, and the level of expression of the mRNAs of growth factors was determined using RT-PCR.

RESULTS

Histopathologic examination revealed degenerative changes in the glomeruli, loss of tubular architecture, loss of brush border, and interrupted tubular basal laminae. These changes were more noticeable in groups treated with 30 and 125 mg/kg. The collagen intensity increased in the group treated with 30 mg/kg in both the cortex and the medulla. Apoptosis was much more evident in middle-dose groups (i.e., 125 and 300 mg/kg). The results of RT-PCR indicated that Bcl-2 and Bax mRNAs upregulated in the treated groups (p < 0.05). Moreover, the data related to EGF, TNF-α, and TGF-β1 revealed that AgNPs induced significant changes in gene expression in the groups treated with 30 and 700 mg/kg compared to the control group.

CONCLUSION

Our observations showed that AgNPs played a critical role in in vivo renal toxicity.

摘要

背景

银纳米粒子(AgNPs)经口服暴露后会在各种器官中蓄积。本研究的主要目的是评估 AgNPs 经重复口服暴露后引起的肾毒性,并确定相关的分子机制。

方法

在这项研究中,将 40 只雄性 Wistar 大鼠用含 30、125、300 和 700mg/kg 的 AgNPs 的溶液处理。暴露 28 天后,用苏木精-伊红(H&E)、马松三色和过碘酸-Schiff(PAS)染色评估组织病理学变化。用 TUNEL 和 caspase-3 的免疫组织化学法量化细胞凋亡,并用 RT-PCR 测定生长因子 mRNA 的表达水平。

结果

组织病理学检查显示肾小球出现退行性变化、肾小管结构丧失、刷状缘丢失和肾小管基底膜中断。在 30 和 125mg/kg 处理组中,这些变化更为明显。在 30mg/kg 处理组中,皮质和髓质中的胶原强度增加。在中剂量组(即 125 和 300mg/kg)中,细胞凋亡更为明显。RT-PCR 结果表明,处理组中 Bcl-2 和 BaxmRNA 上调(p<0.05)。此外,与 EGF、TNF-α和 TGF-β1 相关的数据表明,与对照组相比,30 和 700mg/kg 处理组的 AgNPs 诱导了基因表达的显著变化。

结论

我们的观察结果表明,AgNPs 在体内肾毒性中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/32e1763a2457/12882_2021_2428_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/2aa6c2313d9e/12882_2021_2428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/5c144eb5ddac/12882_2021_2428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/32cba748692b/12882_2021_2428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/5eb36bc68a99/12882_2021_2428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/43674dd17298/12882_2021_2428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/1489c8ef33a5/12882_2021_2428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/1f91e48ccff8/12882_2021_2428_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/32e1763a2457/12882_2021_2428_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/2aa6c2313d9e/12882_2021_2428_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/5c144eb5ddac/12882_2021_2428_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/32cba748692b/12882_2021_2428_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/5eb36bc68a99/12882_2021_2428_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/43674dd17298/12882_2021_2428_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/1489c8ef33a5/12882_2021_2428_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/1f91e48ccff8/12882_2021_2428_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/8212496/32e1763a2457/12882_2021_2428_Fig8_HTML.jpg

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