Evaluation of neurotoxicity and the role of oxidative stress of cobalt nanoparticles, titanium dioxide nanoparticles, and multiwall carbon nanotubes in Caenorhabditis elegans

Abstract 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. Graphical Abstract Graphical Abstract. Nanomaterials induce neurotoxicity via the generation of reactive oxygen species. Survival, locomotion behaviors, and acetylcholinesterase (AchE) activity are reduced when exposed to 3 kinds of nanomaterials, ie, cobalt nanoparticles (CoNPs), titanium dioxide nanoparticles (TiO2-NPs), and multiwall carbon nanotubes (MWCNTs). The activation of glutathione S-transferase-4 (gst-4) was induced by both CoNPs and MWCNTs. Although TiO2-NPs failed to activate gst-4, its exposure generates excessive reactive oxygen species (ROS). Pretreatment of N-acetyl-l-cysteine (NAC) alleviates oxidative stress and the activation of gst-4 induced by nanomaterials, followed by the recovery of survival and locomotion behaviors.