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双面纳米氧化锌:在斑马鱼胚胎中具有卓越的抗菌性能及诱导的肝毒性

Double-Sided Nano-ZnO: Superior Antibacterial Properties and Induced Hepatotoxicity in Zebrafish Embryos.

作者信息

He Mingyue, Li Xueting, Yu Lidong, Deng Shuai, Gu Ning, Li Li, Jia Jianbo, Li Bingsheng

机构信息

School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.

School of Physics, Harbin Institute of Technology, Harbin 150080, China.

出版信息

Toxics. 2022 Mar 18;10(3):144. doi: 10.3390/toxics10030144.

Abstract

Zinc oxide nanoparticles (Nano-ZnO) have been widely used in the food, cosmetics, and biomedical fields due to their excellent antibacterial and antioxidant properties. However, with the widespread application of Nano-ZnO, Nano-ZnO inevitably enters the environment and living organisms, causing harm to human health and ecosystem safety. Therefore, the biosafety and toxicological issues of Nano-ZnO are gradually being emphasized. Our study found that Nano-ZnO has superior antibacterial properties compared to ofloxacin in the fight against (). Given that ofloxacin can inhibit bacterial-induced inflammation, we constructed a model of bacterial inflammation using in zebrafish. We found that Nano-ZnO inhibited the NF-κB-mediated inflammatory signaling pathway. However, in the process, we found that Nano-ZnO caused hepatic steatosis in zebrafish. This suggested that Nano-ZnO had a certain hepatotoxicity, but did not affect liver development. Subsequently, we investigated the mechanism of hepatotoxicity produced by Nano-ZnO. Nano-ZnO triggered oxidative stress in the liver by generating ROS, which then induced endoplasmic reticulum stress to occur. It further activated and its downstream genes and , which promoted the accumulation of fatty acid synthesis and the development of steatosis, leading to the development of nonalcoholic fatty liver disease (NAFLD). To address the hepatotoxicity of Nano-ZnO, we added carbon dots for the treatment of NAFLD. The carbon dots were found to normalize the steatotic liver. This provided a new strategy to address the hepatotoxicity caused by Nano-ZnO. In this work, we systematically analyzed the antibacterial advantages of Nano-ZnO in vivo and in vitro, explored the mechanism of Nano-ZnO hepatotoxicity, and proposed a new method to treat Nano-ZnO hepatotoxicity.

摘要

氧化锌纳米颗粒(纳米氧化锌)因其优异的抗菌和抗氧化性能而被广泛应用于食品、化妆品和生物医学领域。然而,随着纳米氧化锌的广泛应用,纳米氧化锌不可避免地进入环境和生物体,对人类健康和生态系统安全造成危害。因此,纳米氧化锌的生物安全性和毒理学问题逐渐受到重视。我们的研究发现,在对抗()方面,纳米氧化锌比氧氟沙星具有更优异的抗菌性能。鉴于氧氟沙星可以抑制细菌诱导的炎症,我们利用斑马鱼构建了细菌炎症模型。我们发现纳米氧化锌抑制了核因子κB介导的炎症信号通路。然而,在此过程中,我们发现纳米氧化锌导致斑马鱼肝脏脂肪变性。这表明纳米氧化锌具有一定的肝毒性,但不影响肝脏发育。随后,我们研究了纳米氧化锌产生肝毒性的机制。纳米氧化锌通过产生活性氧引发肝脏氧化应激,进而诱导内质网应激发生。它进一步激活了()及其下游基因()和(),促进脂肪酸合成的积累和脂肪变性的发展,导致非酒精性脂肪性肝病(NAFLD)的发生。为了解决纳米氧化锌的肝毒性问题,我们添加碳点来治疗NAFLD。发现碳点可使脂肪变性的肝脏恢复正常。这为解决纳米氧化锌引起的肝毒性提供了一种新策略。在这项工作中,我们系统地分析了纳米氧化锌在体内和体外的抗菌优势,探索了纳米氧化锌肝毒性的机制,并提出了一种治疗纳米氧化锌肝毒性的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cc7/8950655/7eb2fce235ab/toxics-10-00144-g001.jpg

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