Pristimerin Alleviates Nanoparticulate Titanium Dioxide-Triggered Neurodegeneration in Hippocampal and Cortex by Downregulation of Inflammation and Oxidative Damage.

The utilization and toxicity of titanium have become global concerns, primarily owing to the increasing prevalence of titanium dioxide nanoparticles (TNPs) in the environment. The toxicity of TNPs is pivotal in the pathophysiology of neurodegenerative diseases, which are characterized by the formation of neuritic plaques and neurofibrillary tangle associated with Alzheimer's disease (AD). This study assessed behavioral changes in mice triggered by TNPs, focusing on β-amyloid aggregation, DNA damage, inflammation, oxidative stress (OS), and histopathological abnormalities. In addition, the neuroprotective efficacy of pristimerin (PST) against TNP-induced neurotoxicity was evaluated. Mice were orally administered TNPs (5 mg/kg body weight) and treated with PST (12 mg/kg body weight) for 65 days. Spatial working memory was assessed using object recognition, Morris water maze, T-, and Y-maze evaluations. TNPs markedly increased β-amyloid accumulation, altered cytokine levels, heightened DNA damage, decreased antioxidant enzymatic activity, and elevated OS while impairing cognitive memory capacity in the murine brain cortex (CTX) and hippocampus (HPC). In conclusion, TNPs may exhibit significant neurotoxicity following exposure, and PST may serve as a potential protective mechanism against neuronal degeneration.