With the rapid progress of nanotechnology, various nanoparticles (NPs) have been applicated in our daily life. In the field of nanotechnology, metal-based NPs are an important component of engineered NPs, including metal and metal oxide NPs, with a variety of biomedical applications. However, the unique physicochemical properties of metal-based NPs confer not only promising biological effects but also pose unexpected toxic threats to human body at the same time. For safer application of metal-based NPs in humans, we should have a comprehensive understanding of NP toxicity. In this review, we summarize our current knowledge about metal-based NPs, including the physicochemical properties affecting their toxicity, mechanisms of their toxicity, their toxicological assessment, the potential strategies to mitigate their toxicity and current status of regulatory movement on their toxicity. Hopefully, in the near future, through the convergence of related disciplines, the development of nanotoxicity research will be significantly promoted, thereby making the application of metal-based NPs in humans much safer.

The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self‐renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self‐renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N‐acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ‐induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ‐induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC‐pretreated cells showed increased anti‐apoptotic protein Bcl‐2 and decreased pro‐apoptotic protein Bax expression. Similarly, NAC pretreatment increased p‐mTOR and decreased LC3B‐II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ‐induced mNPC self‐renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ‐related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress‐associated toxicants.

Paraquat (PQ) is an agricultural chemical used worldwide. As a potential neurotoxicant, PQ adversely affects neurogenesis and inhibits proliferation of neural progenitor cells (NPCs). However, the molecular mechanistic insights of PQ exposure on NPCs remains to be determined. Herein, we determine the extent to which Wnt/β-catenin signaling involved in the inhibition effect of PQ on mouse NPCs from subventricular zone (SVZ). NPCs were treated with different concentrations of PQ (40, 80, and 120 μM). PQ exposure provoked oxidative stress and apoptosis and PQ inhibited cell viability and proliferation in a concentration-dependent manner. Significantly, PQ exposure altered the expression/protein levels of the Wnt pathway genes in NPCs. In addition, PQ reduced cellular β-catenin, p-GSK-3β, and cyclin-D1 and increased the radio of Bax/Bcl2. Further, Wnt pathway activation by treatment with LiCl and Wnt1 attenuated PQ-induced inhibition of mNPCs proliferation. Antioxidant (NAC) treatment alleviated the inhibition of PQ-induced Wnt signaling pathway. Overall, our results suggest significant inhibitory effects of PQ on NPCs proliferation via the Wnt/β-catenin signaling pathway. Interestingly, our results implied that activation of Wnt/β-catenin signaling pathway attenuated PQ-induced autophagic cell death. Our results therefore bring our understanding of the molecular mechanisms of PQ-induced neurotoxicity.

Cadmium (Cd) is a toxic heavy metal widely found in the environment. Cd is also a potential neurotoxicant, and its exposure is associated with impairment of cognitive function. However, the underlying mechanisms by which Cd induces neurotoxicity are unclear. In this study, we investigated the in vitro effect of Cd on primary murine neural stem/progenitor cells (mNS/PCs) isolated from the subventricular zone. Our results show that Cd exposure leads to mNS/PCs G1/S arrest, promotes cell apoptosis, and inhibits cell proliferation. In addition, Cd increases intracellular and mitochondrial reactive oxygen species (ROS) that activates mitochondrial oxidative stress, decreases ATP production, and increases mitochondrial proton leak and glycolysis rate in a dose‐dependent manner. Furthermore, Cd exposure decreases phosphorylation of protein kinase B (AKT) and glycogen synthase kinase‐3 beta (GSK3β) in mNS/PCs. In addition, pretreatment mNS/PCs with MitoTEMPO, a mitochondrial‐targeted antioxidant, improves mitochondrial morphology and functions and attenuates Cd‐induced inhibition of mNS/PCs proliferation. It also effectively reverses Cd‐induced changes of phosphorylation of AKT and the expression of β‐catenin and its downstream genes. Taken together, our data suggested that AKT/GSK3β/β‐catenin signaling pathway is involved in Cd‐induced mNS/PCs proliferation inhibition via MitoROS‐dependent pattern.