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

Abstract

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.

Keywords: chitosan; nanoparticles; neurotoxicity; titanium dioxide.