ZIF-8 nanoparticles induce neurobehavioral disorders through the regulation of ROS-mediated oxidative stress in zebrafish embryos. (October 2022)

• Record Type: Journal Article
• Authors: Hu, Hongmei; Su, Meile; Ba, Huixia; Chen, Guilan; Luo, Jiaqi; Liu, Fasheng; Liao, Xinjun; Cao, Zigang; Zeng, Junquan; Lu, Huiqiang; Xiong, Guanghua; Chen, Jianjun
• Is Part Of: Chemosphere. Volume 305(2022)
• Publication Date: 2022-10
• Subjects: ZIF-8 -- Neurotoxicity -- Locomotor behavior -- Neuroinflammation -- Oxidative stress -- Zebrafish; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.135453
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Zeolite imidazolate framework-8 (ZIF-8) is a nanomaterial of metal-organic frameworks (MOFs), which have various applications in drug delivery and water pollution remediation. However, little is known about its developmental neurotoxicity in aquatic organisms, especially on the low-level exposure. In the present study, we investigated the toxic effects of ZIF-8 NPs on the neuron development, behavioral traits, oxidative stress and gene expression in zebrafish embryos. Firstly, our results showed that ZIF-8 induced significantly embryonic malformations and abnormal development of nervous system in zebrafish embryos with a concentration-dependent manner. Meanwhile, the locomotor behavior was obviously inhibited while the anxiety behavior was greatly increased after ZIF-8 exposure. Secondly, the levels of ROS and antioxidant enzyme activities (CAT, SOD and MDA) together with AChE and ATPase were substantially increased in the ZIF-8 exposed groups. At the molecular level, ZIF-8 NPs could down-regulate the expression profiles of neural development-related genes (gap43, synapsin 2a and neurogenin 1) and PD-like related genes (dj-1, dynactin and parkin), but up-regulate the expression levels of neuro-inflammatory genes (nox-1, glip1a and glip1b) in larval zebrafish. In addition, we further explored the molecular mechanism of neurotoxicity induced by ZIF-8 with pharmacological experiments. The results showed that specific inhibition of ROS-mediated oxidative stress by the astaxanthin could reverse the expression patterns of ATPase, AChE and neurodevelopmental genes. Moreover, astaxanthin can partially rescue the ZIF-8-modulated locomotor behavior. Taken together, our results demonstrated that ZIF-8 had the potential to cause neurotoxicity in zebrafish embryos. These informations presented in this study will help to elucidate the molecular mechanisms of ZIF-8 nanoparticles exposure in zebrafish, which providing a scientific evaluation of its safety to aquatic ecosystems. Graphical abstract: Image 1 Highlights: ZIF-8 nanoparticles induced developmental neurotoxicity in zebrafish. ZIF-8 NPs could increase the levels of oxidative stress and neuro-inflammatory genes. ZIF-8 exposure could markedly decrease the locomotor behavior and increase the anxiety behavior. Inhibition of ROS by astaxanthin can partially rescue the ZIF-8 induced neurobehavioral disorders.