Investigating the Impact of Zinc Oxide Nanoparticles and Folic Acid on Neuronal Markers in a Rat Model of Nanotoxicity

Exposure to zinc oxide nanoparticles (ZnONPs) is more likely due to their wide utilization in the food and pharmaceutical sectors. Therefore, serum neuromarkers and hippocampal tissue were examined for the potential prophylactic impact of folic acid in four groups of rats, each consisting of 10 animals. The first group had 150 mg/kg ZnONPs orally every day for 2 weeks. The second group received 10 mg/kg of folic acid intraperitoneal (ip) for 1 week, followed by ZnONPs daily for 2 weeks. The third group received folic acid only, while the control group was given distilled water. At the end of the experiments, hippocampi were examined, and serum concentrations were measured for glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), monoamine oxidase A (MAOA), and neurofilament light polypeptide (NEFL). ZnONPs-exposed animals exhibited significantly lower levels of GFAP and MBP (<i>p</i> < 0.05 and <i>p</i> < 0.001, respectively) compared to all groups, while the same overdosed animals showed significantly higher levels of MAOA compared to the group that received folic acid prophylaxis (<i>p</i> < 0.001). NEFL levels did not significantly differ among all groups. Histopathological analysis revealed neurodegeneration in the ZnONPs-exposed group, characterized by neuronal shrinkage, hyperchromatic nuclei, vacuolated cytoplasm, and cell loss. Folic acid partially mitigated these effects, preserving Nissl granules and reducing pyknotic changes, though some ghost cells persisted. In summary, the positive impact of folic acid on reducing ZnONPs toxicity is promising to be further investigated as a preventive measure against nanoparticle-induced neurotoxicity.