Zinc Oxide Nanoparticle–Induced Neurotoxicity

Abstract

Background: Zinc oxide nanoparticles (ZnO-NPs) are increasingly incorporated into industrial, pharmaceutical, and cosmetic products due to their antimicrobial, UV-blocking, and catalytic properties. However, their small size and high reactivity raise safety concerns, particularly regarding their potential to cross biological barriers and exert toxic effects on the central nervous system. Accumulating evidence indicates that ZnO-NPs may induce neurotoxicity through oxidative stress, inflammation, and cellular dysfunction, necessitating a systematic understanding of their mechanisms of action. Objective: This study aims to summarize and analyze current evidence on the neurotoxic effects of ZnO-NPs, focusing on the mechanisms of neuronal damage, behavioral alterations, and the role of physicochemical characteristics influencing toxicity. Methods: A comprehensive review of peer-reviewed studies published in recent years was conducted using databases such as PubMed, ScienceDirect, and Scopus. Both in vitro and in vivo studies investigating ZnO-NP exposure and neurotoxic outcomes were included. Data were synthesized to evaluate oxidative stress markers, inflammatory mediators, neurotransmitter alterations, and histopathological changes in brain tissues. Results: Findings reveal that ZnO-NPs can readily penetrate the blood–brain barrier and accumulate in neural tissues. Exposure results in increased reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial dysfunction, and neuronal apoptosis. Neuroinflammatory responses are characterized by elevated cytokines such as TNF-α and IL-6. In animal models, ZnO-NP exposure leads to behavioral changes including memory deficits, anxiety-like behavior, and impaired motor coordination. The degree of neurotoxicity correlates with nanoparticle size, concentration, surface charge, and exposure duration. Dissolved Zn²⁺ ions also contribute significantly to the observed cytotoxicity. Conclusion: Zinc oxide nanoparticles exhibit dose-dependent neurotoxic effects mediated by oxidative stress, inflammation, and apoptosis. While these findings highlight potential risks associated with widespread ZnO-NP use, further studies are required to establish safe exposure thresholds and to explore strategies such as surface modification to reduce neurotoxic potential. Understanding these mechanisms will be crucial in guiding the safe design and application of nanomaterials in consumer and biomedical products. Keywords: Zinc oxide nanoparticles, neurotoxicity, oxidative stress, apoptosis, inflammation, blood–brain barrier, nanotoxicology.