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The role of hypoxia-inducible factor-1α in zinc oxide nanoparticle-induced nephrotoxicity in vitro and in vivo

Overview of attention for article published in Particle and Fibre Toxicology, September 2016
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Title
The role of hypoxia-inducible factor-1α in zinc oxide nanoparticle-induced nephrotoxicity in vitro and in vivo
Published in
Particle and Fibre Toxicology, September 2016
DOI 10.1186/s12989-016-0163-3
Pubmed ID
Authors

Yuh-Feng Lin, I-Jen Chiu, Fong-Yu Cheng, Yu-Hsuan Lee, Ying-Jan Wang, Yung-Ho Hsu, Hui-Wen Chiu

Abstract

Zinc oxide nanoparticles (ZnO NPs) are used in an increasing number of products, including rubber manufacture, cosmetics, pigments, food additives, medicine, chemical fibers and electronics. However, the molecular mechanisms underlying ZnO NP nephrotoxicity remain unclear. In this study, we evaluated the potential toxicity of ZnO NPs in kidney cells in vitro and in vivo. We found that ZnO NPs were apparently engulfed by the HEK-293 human embryonic kidney cells and then induced reactive oxygen species (ROS) generation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of apoptosis and autophagy. Interestingly, the ROS-induced hypoxia-inducible factor-1α (HIF-1α) signaling pathway was significantly increased following ZnO NPs exposure. Additionally, connective tissue growth factor (CTGF) and plasminogen activator inhibitor-1 (PAI-1), which are directly regulated by HIF-1 and are involved in the pathogenesis of kidney diseases, displayed significantly increased levels following ZnO NPs exposure in HEK-293 cells. HIF-1α knockdown resulted in significantly decreased levels of autophagy and increased cytotoxicity. Therefore, our results suggest that HIF-1α may have a protective role in adaptation to the toxicity of ZnO NPs in kidney cells. In an animal study, fluorescent ZnO NPs were clearly observed in the liver, lungs, kidneys, spleen and heart. ZnO NPs caused histopathological lesions in the kidney and increase in serum creatinine and blood urea nitrogen (BUN) which indicate possible renal possible damage. Moreover, ZnO NPs enhanced the HIF-1α signaling pathway, apoptosis and autophagy in mouse kidney tissues. ZnO NPs may cause nephrotoxicity, and the results demonstrate the importance of considering the toxicological hazards of ZnO NP production and application, especially for medicinal use.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 49 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 16%
Student > Master 7 14%
Student > Bachelor 6 12%
Student > Doctoral Student 5 10%
Professor > Associate Professor 5 10%
Other 7 14%
Unknown 12 24%
Readers by discipline Count As %
Medicine and Dentistry 9 18%
Biochemistry, Genetics and Molecular Biology 5 10%
Chemistry 5 10%
Agricultural and Biological Sciences 5 10%
Environmental Science 4 8%
Other 9 18%
Unknown 13 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 September 2016.
All research outputs
#20,342,896
of 22,889,074 outputs
Outputs from Particle and Fibre Toxicology
#462
of 561 outputs
Outputs of similar age
#280,134
of 322,819 outputs
Outputs of similar age from Particle and Fibre Toxicology
#11
of 18 outputs
Altmetric has tracked 22,889,074 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 561 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 322,819 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.