Chitosan attenuated the neurotoxicity-induced titanium dioxide nanoparticles in brain of adult rats

In the current study, we aimed to investigate the neurotoxic effect of oral titanium dioxide nanoparticles (TiO2 NPs) as well as the possible neuroprotective effect of carboxymethyl chitosan in adult rats for 14 days. The results revealed that TiO2 NPs inhibited the activity of the acetylcholine esterase enzyme and the levels of serotonin, dopamine, and norepinephrine neurotransmitters. Additionally, it induced neuro-oxidative stress and neuroinflammation via an elevation in MDA levels and IL-6, while GSH concentration, as well as GPx and GST activities, were decreased. TiO2 NPs induced neuronal apoptosis through upregulation of the expression of caspase-8 and -9 that was further confirmed by increasing caspases-3 and -8 proteins in the hippocampus, cerebral cortex, and cerebellum. The expression of the immediate-early gene BDNF was increased in response to TiO2 NPs, while that of Arc was reduced. Chitosan significantly attenuated the TiO2 NPs-induced neurotoxicity regarding AChE, serotonin, MDA, GSH, GPx, GST, IL-6, caspases-8, -9, and -3. Chitosan inhibited the expression of Arc and alleviated the effect of TiO2 NPs on BDNF expression. Collectively, TiO2 NPs induced neurotoxicity via their action on vital neuronal biomarkers that might in turn cause brain dysfunction. Despite the neuroprotection of chitosan, its inhibitory effect on Arc expression should be considered.

Automated summary

The study demonstrated that titanium dioxide nanoparticles induce neurotoxicity by affecting various neuronal biomarkers, leading to neuronal damage and apoptosis. While chitosan shows neuroprotective effects, its inhibitory effect on Arc expression should be taken into consideration.