Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province 350122, China.
Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, Fujian Province 350122, China.
Toxicol Sci. 2023 Oct 30;196(1):85-98. doi: 10.1093/toxsci/kfad084.
The widespread use of nanomaterials in daily life has led to increased concern about their potential neurotoxicity. Therefore, it is particularly important to establish a simple and reproducible assessment system. Representative nanomaterials, including cobalt nanoparticles (CoNPs), titanium dioxide nanoparticles (TiO2-NPs), and multiwall carbon nanotubes (MWCNTs), were compared in terms of their neurotoxicity and underlying mechanisms. In 0, 25, 50, and 75 μg/ml of these nanomaterials, the survival, locomotion behaviors, acetylcholinesterase (AchE) activity, reactive oxygen species production, and glutathione-S transferase 4 (Gst-4) activation in wildtype and transgenic Caenorhabditis elegans (C. elegans) were evaluated. All nanomaterials induced an imbalance in oxidative stress, decreased the ratio of survival, impaired locomotion behaviors, as well as reduced the activity of AchE in C. elegans. Interestingly, CoNPs and MWCNTs activated Gst-4, but not TiO2-NPs. The reactive oxygen species scavenger, N-acetyl-l-cysteine, alleviated oxidative stress and Gst-4 upregulation upon exposure to CoNPs and MWCNTs, and rescued the locomotion behaviors. MWCNTs caused the most severe damage, followed by CoNPs and TiO2-NPs. Furthermore, oxidative stress and subsequent activation of Gst-4 were involved in nanomaterials-induced neurotoxicity. Our study provides a comprehensive comparison of the neurotoxicity and mechanisms of typical nanomaterials, which could serve as a model for hazard assessment of environmental pollutants using C. elegans as an experimental model system.
纳米材料在日常生活中的广泛应用,导致人们对其潜在神经毒性的关注度日益增加。因此,建立一个简单且可重复的评估系统尤为重要。本研究比较了钴纳米粒子(CoNPs)、二氧化钛纳米粒子(TiO2-NPs)和多壁碳纳米管(MWCNTs)等典型纳米材料的神经毒性及其潜在机制。在 0、25、50 和 75μg/ml 这些纳米材料中,评估了野生型和转基因秀丽隐杆线虫(C. elegans)的存活率、运动行为、乙酰胆碱酯酶(AchE)活性、活性氧(ROS)的产生和谷胱甘肽 S-转移酶 4(Gst-4)的激活情况。所有纳米材料均导致氧化应激失衡,降低存活率,损害运动行为,并降低 C. elegans 中的 AchE 活性。有趣的是,CoNPs 和 MWCNTs 激活了 Gst-4,但 TiO2-NPs 没有。ROS 清除剂 N-乙酰-L-半胱氨酸(N-acetyl-l-cysteine)缓解了 CoNPs 和 MWCNTs 暴露引起的氧化应激和 Gst-4 上调,并挽救了运动行为。MWCNTs 造成的损伤最严重,其次是 CoNPs 和 TiO2-NPs。此外,氧化应激和随后的 Gst-4 激活参与了纳米材料诱导的神经毒性。本研究全面比较了典型纳米材料的神经毒性和机制,为利用 C. elegans 作为实验模型系统评估环境污染物的危害提供了参考。