Surface modification as a strategy to mitigate TiO₂ NPs-induced neurotoxicity in rats

Titanium dioxide nanoparticles (TiO₂ 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 TiO₂ 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 TiO₂ NPs (100 mg/kg bwt); CS/TiO₂ NPs (100 mg/kg bwt), and Si/TiO₂ NPs (100 mg/kg bwt). All rats received daily treatments via oral gavage for a period of 2 months. The uncoated TiO₂ 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 TiO₂ NPs with either CS or Si significantly mitigated the biochemical, molecular, histopathological, and behavioral alterations compared to the uncoated TiO₂ NPs.