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Inhibition of inhaled halloysite nanotube toxicity by trehalose through enhanced autophagic clearance of p62.
Nanotoxicology ( IF 5 ) Pub Date : 2019-02-01 , DOI: 10.1080/17435390.2018.1549688
Rui Rong 1 , Yongming Zhang 1 , Yunjiao Zhang 2 , Yi Hu 3 , Wenjie Yang 1 , Xiaowen Hu 4 , Longping Wen 3 , Qixing Zhang 1
Affiliation  

Nanomaterials are widely used in an ever-increasing number of consumer and industrial products. It is therefore essential that the toxic effects of nanomaterials are understood in order to improve product safety. Here we evaluate the toxicity of inhaled halloysite nanotubes (HNTs) by applying a purpose designed inhalation exposure system and succeed in suppressing HNTs toxicity using trehalose. By assessing apoptosis, oxidative stress, inflammatory response, and autophagy, it is found that HNTs can cause sub-chronic toxicity in mice. Further investigations indicate that HNTs induce autophagy blockade that results in the accumulation of sequestosome-1 (p62), which is responsible for the excessive apoptosis, inflammatory response and oxidative stress. We found that p62 can be eliminated by trehalose and the application of trehalose in vitro and in vivo successfully inhibits toxicity by accelerating the clearance of p62. Trehalose shows great potential for reducing nanoparticle toxicity.

中文翻译:

通过增强p62的自噬清除作用,海藻糖可抑制吸入的埃洛石纳米管毒性。

纳米材料广泛用于越来越多的消费和工业产品中。因此,必须了解纳米材料的毒性作用,以提高产品安全性。在这里,我们通过应用专门设计的吸入暴露系统评估吸入的埃洛石纳米管(HNTs)的毒性,并成功地使用海藻糖抑制HNTs的毒性。通过评估细胞凋亡,氧化应激,炎症反应和自噬,发现HNTs可在小鼠中引起亚慢性毒性。进一步的研究表明,HNTs诱导自噬阻滞,导致sequestosome-1(p62)的积累,这是造成过度凋亡,炎症反应和氧化应激的原因。我们发现海藻糖可以消除p62,海藻糖在体内和体外的应用通过加速p62的清除而成功地抑制了毒性。海藻糖显示出降低纳米颗粒毒性的巨大潜力。
更新日期:2019-02-01
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