Elhussein_2026_Toxicol.Appl.Pharmacol__118024

Titanium dioxide nanoparticles (TiO NPs) are extensively utilized in biomedical and pharmacological sectors; however, they may interact with biological systems causing various risks. Therefore, the present study assessed the role of surface modification by either chitosan (CS) or silica (Si) in mitigating TiO NPs-induced neurotoxicity in rats. A total of twenty adult male rats were randomly distributed into 4 experimental groups (n = 5) as follows: control; uncoated TiO NPs (100 mg/kg bwt); CS/TiO NPs (100 mg/kg bwt), and Si/TiO NPs (100 mg/kg bwt). All rats received daily treatments via oral gavage for a period of 2 months. The uncoated TiO NPs elicited pronounced neurobehavioral disturbances, including cognitive disruption, memory impairment, and heightened anxiety, associated with increased acetylcholinesterase (AChE) activity, malondialdehyde (MDA), and nitric oxide (NO) levels, while reduced antioxidant activity. A pronounced upregulation of caspase-3 with downregulation of Nrf2 and Bdnf genes was also observed alongside strong immunoreactivity of caspase-3, iNOS, and GFAP in many brain areas, indicating neurodegenerative and inflammatory responses. In contrast, the encapsulation of TiO NPs with either CS or Si significantly mitigated the biochemical, molecular, histopathological, and behavioral alterations compared to the uncoated TiO(2) NPs.