Exploring Oxidative Stress Mechanisms of Nanoparticles Using Zebrafish (): Toxicological and Pharmaceutical Insights.

Nanoparticles (NPs) have revolutionized biomedical and pharmaceutical applications due to their unique physicochemical properties. However, their widespread use has raised concerns regarding their potential toxicity, particularly mediated by oxidative stress mechanisms. This redox imbalance, primarily driven by the overproduction of reactive oxygen species (ROS), plays a central role in NP-induced toxicity, leading to cellular dysfunction, inflammation, apoptosis, and genotoxicity. Zebrafish () have emerged as a powerful in vivo model for nanotoxicology, offering advantages such as genetic similarity to humans, rapid development, and optical transparency, allowing real-time monitoring of oxidative damage. This review synthesizes current findings on NP-induced oxidative stress in zebrafish, highlighting key toxicity mechanisms and case studies involving metallic (gold, silver, copper), metal oxide (zinc oxide, titanium dioxide, iron oxide), polymeric, and lipid-based NPs. The influence of NP physicochemical properties, such as size, surface charge, and functionalization, on oxidative stress responses is explored. Additionally, experimental approaches used to assess ROS generation, antioxidant enzyme activity, and oxidative damage biomarkers in zebrafish models are examined. In addition to toxicity concerns, pharmaceutical applications of antioxidant-modified NPs are evaluated, particularly their potential in drug delivery, neuroprotection, and disease therapeutics. Notably, studies show that curcumin- and quercetin-loaded nanoparticles enhance antioxidant defense and reduce neurotoxicity in zebrafish models, demonstrating their promise in neuroprotective therapies. Furthermore, cerium oxide nanoparticles, which mimic catalase and SOD enzymatic activity, have shown significant efficacy in reducing ROS and protecting against oxidative damage. Challenges in zebrafish-based nanotoxicology, the need for standardized methodologies, and future directions for optimizing NP design to minimize oxidative stress-related risks are also discussed. By integrating insights from toxicity mechanisms, case studies, and pharmaceutical strategies, this review supports the development of safer and more effective nanoparticle-based therapies while addressing the challenges of oxidative stress-related toxicity.