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氧化钇纳米颗粒对人胚肾细胞293的细胞毒性和遗传毒性

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells.

作者信息

Selvaraj Vellaisamy, Bodapati Sravanthi, Murray Elizabeth, Rice Kevin M, Winston Nicole, Shokuhfar Tolou, Zhao Yu, Blough Eric

机构信息

Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA.

Department of Integrated Science and Technology, Marshall University, Huntington, WV, USA.

出版信息

Int J Nanomedicine. 2014 Mar 12;9:1379-91. doi: 10.2147/IJN.S52625. eCollection 2014.

Abstract

BACKGROUND

The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0-50 μg/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y2O3) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant.

RESULTS

The 24-hour inhibitory concentration 50 (IC50) of Y2O3 NPs (41 ± 5 nm in size) in the HEK293 cells was found to be 108 μg/mL. Incubation with Y2O3 NPs (12.25-50 μg/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response.

CONCLUSION

These data demonstrate that the Y2O3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells.

摘要

背景

工程纳米颗粒(NPs)使用的增加引发了对生物系统潜在暴露以及这些材料可能对人类健康构成的潜在风险的新担忧。在此,我们研究了暴露于不同浓度(0 - 50μg/mL)和孵育时间(10小时、24小时或48小时)的氧化钇(Y2O3)纳米颗粒对人胚肾(HEK293)细胞的影响。将纳米颗粒暴露后细胞形态、细胞活力、细胞膜完整性、活性氧水平、线粒体膜电位、细胞死亡(凋亡和坏死)以及DNA损伤的变化与用百草枯(一种已知的有毒物质)孵育后的影响进行了比较。

结果

发现Y2O3纳米颗粒(尺寸为41±5nm)在HEK293细胞中的24小时半数抑制浓度(IC50)为108μg/mL。用Y2O3纳米颗粒(12.25 - 50μg/mL)孵育以浓度和时间依赖性方式增加了Bax/Bcl - 2比值、caspase - 3表达,并促进了凋亡和坏死介导的细胞死亡。细胞存活率的降低与细胞活性氧水平升高、线粒体膜通透性增加以及DNA损伤证据相关,这与线粒体损伤可能在细胞毒性反应中起重要作用的可能性一致。

结论

这些数据表明,暴露于Y2O3纳米颗粒与培养的HEK293细胞中细胞凋亡和坏死增加有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a84/3958544/4d9a75b4074b/ijn-9-1379Fig1.jpg

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