The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administration of saffron extract, in rats, can protect from neurotoxicity and behavioural disturbances induced by chronic administration of ZnO‐NPs. Daily oral administration of ZnO‐NPs was performed for 21 consecutive days to induce oxidative stress‐like situation. Then after the saffron extract was concomitantly administrated in several rat groups to overcome the nanotoxicological effect induced by ZnO‐NPs. In the frontal cortex, the hippocampus and the cerebellum, ZnO‐NPs induced a H2O2‐oxydative stress‐like effect reflected in reduced enzymatic activities of catalase, superoxide dismutase and glutathione S‐transferase, and decreased acetylcholinesterase activity. In addition, increased levels of proinflammatory interleukins IL‐6 and IL‐1‐⍺ occurred in the hippocampus, reveal the existence of brain inflammation. The concomitant administration of saffron extract to animals exposed to ZnO‐NPs prevented the enhanced anxiety‐related to the behaviour in the elevated plus‐maze test, the open field test and preserved spatial learning abilities in the Morris water maze. Moreover, animals exposed to ZnO‐NPs and saffron showed abnormal activity of several antioxidant enzymes as well as acetylcholinesterase activity, an effect that may underly the preserved anxiety‐like behaviour and spatial learning abilities observed in these animals. Saffron extract has a potential beneficial therapeutic effect: antioxidant, anti‐inflammatory and neuroprotective agent.

Exposure to certain environmental factors and xenobiotic agents can lead to an excess of reactive oxygen species and free radical formation that can damage neuronal cells and affect cognitive function. Silica nanoparticles, as probes for genes or proteins, are already used in nanomedicine as a nanocarrier for several drugs. In the present study, SiO2 NPs were functionalized with glutamate to fight the oxidative-induced stress following chronic exposure to hydrogen peroxide (H2O2). This study aims to investigate whether Glutamate-functionalized Silica Nanoparticles can prevent the neurobehavioral and functional modifications displayed by adult male rats exposed to hydrogen peroxide (H2O2). We observed that subchronic exposure (21 days)to H2O2 induced an anxious state and a decrease in locomotor activity in the animals compared to controls. It the Morris water maze task, rats exposed to H2O2 showed impaired spatial learning and memory abilities. In addition, we observed that compared to controls, H2O2 exposed animals showed an imbalance in the redox status and disturbances of the enzyme’s activities-acetylcholinesterase (AChE) and Monoamine Oxidase (MAO) that were prevented by concomitant SiO2 NPs administration. Furthermore, H2O2 treatment enhanced the occurrence of necrotic and degenerative cell changes in several brain areas (hippocampus, subiculum, caudate-putamen and frontal cortex), that were ameliorated by SiO2 NPs treatment. In summary, the supplementation of L-glutamic acid-functionalized silica Nanoparticles corrected enzymatic activities, reduced behavioral disturbances and diminished histological alterations induced by H2O2. Our results suggest that SiO2 NPs are useful to prevent or ameliorate behavioral impairment, as well as antioxidant enzymatic disturbances and neural damage induced by oxidative stress in the hippocampus and frontal cortex.