The brain has natural antioxidant defense systems, functioning through enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase, which neutralize reactive oxygen species (ROS). Once these defense systems are overwhelmed by poisoning, oxidative damage can occur in the brain. In this study, hydrogen peroxide (H2O2) was used to induce oxidative stress. Ascorbic acid grafted to silica nanoparticles (SiO2-NPs@AA) was used as a therapeutic strategy aimed to reduce ROS levels and enhancing antioxidant defenses. The SiO2-NPs@AA were synthesized and characterized, showing efficient functionalization with ascorbic acid. The in-vitro, antioxidant assays revealed that SiO2-NPs@AA exhibited significant radical scavenging activity (DPPH and hydroxyl radicals) and high iron-chelating ability with enhanced stability compared to free ascorbic acid. Moreover, the in-vivo study demonstrated that SiO2-NPs@AA mitigated H2O2-induced effects in key enzymes, including superoxide dismutase, catalase, glutathione (GSH), and restore acetylcholinesterase (AChE) levels. Notably, malondialdehyde (MDA) levels, a marker of lipid peroxidation, were significantly reestablished in the frontal cortex and hippocampus following SiO2-NPs@AA. Overall, the study revealed that SiO2-NPs@AA corrected effectively nitric oxide (NO) and monoamine oxidase activities, which confirm their role to preserve neuronal function and mitigate neurotoxicity.

SiO2 nanoparticles functionalized with glutamate were investigated for their ability to alleviate oxidative stress caused by prolonged exposure to hydrogen peroxide (H2O2). The study involved ten different groups, each consisting of eight animals, to examine the effects of H2O2 -induced oxidative stress. The results demonstrated that exposure to H2O2 stress oxidative biomarkers were altered accompanied with a loss of spatial learning and memory in rats performing the Morris water maze task. Furthermore, SiO2 nanoparticles functionalized with L-glutamic acid alleviated the H2O2-induced acceleration of necrotic and degenerative cell changes in the hippocampus, subiculum, caudate-putamen, and frontal cortex. Additionally, L-glutamic acid-functionalized SiO2 nanoparticles reduced the redox imbalance and interfered with acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities induced by H2O2.

Oxidative stress is the main manifestation of several neurodegenerative diseases. The same metabolic and behavioral scheme can be seen in neurotoxicity. Several factors are likely to induce oxidative stress. Metallic oxides nanoparticles (NPs) induce the formation of reactive oxygen species, which may seriously affect the brain despite the blood-brain barrier. However, the strategies to protect the brain and/or to restore its physiological equilibrium following neurotoxicity induced by NPs are still under investigation. Here we use eight groups of rats to show how oxidative damage from zinc oxide can be mitigated. The neurotoxicity can be mitigated by the intervention of ascorbic acid (AA) and glutamate (Glu) to restore the activity of the antioxidative system and mitigate the behavioral disorder caused by zinc oxide NPs (ZnO-NPs). Biochemical analysis shows that the administration of ZnO-NPs at 25 mg/Kg causes an oxidative response in the brain which alters the serum biochemical parameters and induces serious disorders in the behavior of animals. The combined treatments using AA and Glu with nanoparticles proved to be corrective at the biochemical level. Using the elevated plus maze (EPM) test, we demonstrated that AA and AA + Glu cure the anxious state and ameliorate the damage to the learning and memory of rats caused by ZnO-NPs.

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 H2 O2 -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.

Abstract 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.

Silver nanoparticles (Ag-NPs) are extremely useful in a diverse range of consumer goods. However, their impact on the environment is still under research, especially regarding the mechanisms involved in their effect. Aiming to provide some insight, the present work analyzes the transcriptional activity of six genes ( Hsp83 , Hsp17.2 , Hsp19.8 , SOD Cu–Zn , Mn-SOD , and BPI ) in the terrestrial snail Helix aspersa in the presence of different concentrations of Ag-NPs. The animals were exposed for seven days to Lactuca sativa soaked for one hour in different concentrations of Ag-NPs (20, 50, 100 mg/L). The results revealed that the highest concentration tested of Ag-NPs (100 mg/L) led to a statistically significant induction of the Hsp83 and BPI expression in the digestive gland compared to the control group. However, a trend to upregulation with no statistical significance was observed for all the genes in the digestive gland and the foot, while in the hemolymph, the trend was to downregulation. Ag-NPs affected the stress response and immunity under the tested conditions, although the impact was weak. It is necessary to explore longer exposure times to confirm that the effect can be maintained and impact on health. Our results highlight the usefulness of the terrestrial snail Helix aspersa as a bioindicator organism for silver nanoparticle pollution biomonitoring and, in particular, the use of molecular biomarkers of pollutant effect as candidates to be included in a multi-biomarker strategy.

Context Titanium dioxide nanoparticles (TiO2-NPs) are used in many commercial products. However, their effects on human and animal organism remained to be clarified.Objective The present study aimed to investigate the effects of TiO2-NPs on the behavioural performance, monoamine neurotransmitters and oxidative stress in the rat brain.Material and methods Rats were injected intravenously with a single dose of TiO2-NPs (20 mg/kg body weight) and were subjected to cognitive and emotional tests using Morris water maze and elevated plus maze.Results Cognitive capacity as well as the emotional reactivity were significantly disrupted, in TiO2-NPs-administered rats compared to control group. These behavioural effects were correlated with changes in brain neurotransmitter contents reflected by a significant increase in dopamine and a decrease in serotonin levels. TiO2-NPs also induced oxidative stress in the brain manifested by increased levels of H2O2 and malondialdehyde, associated with antioxidant enzymes activities disturbance, in particular, superoxide dismutase and catalase activities. Moreover, TiO2-NPs administration caused histological damages in the brain tissue with abundant lymphocytic clusters, capillary dilations, vascular congestion and oedema.Conclusions Acute intravenous injection of TiO2-NPs impaired behaviour performances through brain biochemical and structural changes and precautions should be taken to their usage in food additive and medical applications.

Nanomaterials have gained much attention for their use and benefit in several fields. Iron Oxide Nanoparticles (IONPs) have been used in Biomedicine as contrast agents for imaging cancer cells. However, several studies reported the potential toxicity of those nanoparticles in different models, especially in cells. Therefore, in our present study, we investigated the effects of IONPs on the SH-SY5Y neuroblastoma cell line. We carried out cytotoxic and genotoxic studies to evaluate the phenotypic effects, and proteomic investigation to evaluate the molecular effects and the mechanisms by which this kind of NPs could induce toxicity. Our results showed that the use of three different sizes of IONPs (14, 22 and 30 nm) induced cell detachment, cell morphological changes, size, and concentration-dependent IONP internalization and cell mortality. IONPs induced slight genotoxic damage assayed by modified comet assay without affecting cell cycle, mitochondrial function, membrane integrity, intracellular calcium level, and without inducing ROS generation. All the studies were performed to compare also the effects of IONPs to the ferric iron by incubating cells with equivalent concentration of FeCl3. In all tests, the NPs exhibited more toxicity than the ferric iron. The proteomic analysis followed by gene ontology and pathway analysis evidenced the effects of IONPs on cytoskeleton, cell apoptosis, and cancer development. Our findings provided more information about IONP effects on human cells and especially on cancer cell line.

Iron Oxide Nanoparticles (IONPs) present unique properties making them one of the most used NPs in the biomedical field. Nevertheless, for many years, growing production and use of IONPs are associated with risks that can affect human and the environment. Thus, it is essential to study the effects of these nanoparticles to better understand their mechanism of action and the molecular perturbations induced in the organism. In the present study, we investigated the toxicological effects of IONPs (γ-Fe2O3) on liver, lung and brain proteomes in Wistar rats. Exposed rats received IONP solution during 7 consecutive days by intranasal instillation at a dose of 10 mg/kg body weight. An iTRAQ-based quantitative proteomics was used to study proteomic variations at the level of the three organs. Using this proteomic approach, we identified 1565; 1135 and 1161 proteins respectively in the brain, liver and lung. Amon them, we quantified 1541; 1125 and 1128 proteins respectively in the brain, liver and lung. Several proteins were dysregulated comparing treated samples to controls, particularly, proteins involved in cytoskeleton remodeling, cellular metabolism, immune system stimulation, inflammation process, response to oxidative stress, angiogenesis, and neurodegenerative diseases.

Iron Oxide Nanoparticles (IONPs) are used in several fields of application, mainly in the biomedical field for their magnetic properties and in food additive known as "E172" for their colour. In the present investigation, we focused on IONP effects on Wistar rat following acute oral exposure. We performed a multiscale physiopathological investigation in order to elucidate potential toxic effects linked to IONP ingestion, especially on cognitive capacities, trace element distribution, blood constituents, organ functions, organ structure and iron deposit. We demonstrated that oral exposure to IONPs induces disturbances of certain parameters depending on the dose. Interestingly, the histopathological examination evidenced inflammatory effects of IONPs in the liver with iron deposits in hepatocytes and Kuppfer cells. Neurobehavioral examination showed that oral exposure to IONPs did not affect nor rat emotions, exploration and locomotion capacities, nor spatial reference memory status. Furthermore, oral administration of IONPs did not disrupt the trace element homeostasis nor in the liver neither in the stomach. Altogether, our study evidenced low signs of toxicity, but some effects lead us to a careful use of these NPs. Thereby, their use in foods should be further studied to better evaluate the potential toxic risks of the oral exposure to IONPs.

There is increasing scientific evidences that the physical and chemical properties of manufactured nanoparticles lead to an increase in their bioavailability and toxicity. Among them Copper oxide nanoparticles (CuO-NPs) are widely used in different fields. However their potential adverse effects namely on brain functions are still discussed. Thus, the present study aimed to investigate the subacute oral toxicity and effects of CuO-NPs on cognitive performances in rats. Rats were randomly divided into three groups of 8 animals each, a control group received a dose 9 parts per thousand sodium chloride and the other groups received a suspension of CuO-NPs at doses of 250 and 500 mg/kg through oral gavage for 14 consecutive days. Multiple behavioral tests showed that CuO-NPs caused little changes in memory and learning performances as well as the locomotors activity, while the anxiety index increased. Copper NPs exposure increased also the liver and stomach relative weights and altered some blood biochemical parameters.

Engineered nanomaterials are used in various applications due to their particular properties. Among them, Iron Oxide Nanoparticles (Fe2O3-NPs) are used in Biomedicine as theranostic agents i.e. contrast agents in Magnetic Resonance Imaging and cancer treatment. With the increasing production and use of these Fe2O3-NPs, there is an evident raise of Fe2O3-NPs exposure and subsequently a higher risk of adverse outcomes for the environment and Human. In the present paper, we investigated the effects of an intravenous daily Fe2O3-NPs exposure on Wistar rat for one week. As results, we showed that several hematological parameters and transaminase (ALT and AST) levels as well as organ histology remained unchanged in treated rats. Neither the catecholamine levels nor the emotional behavior and learning / memory capacities of rats were impacted by the sub-acute intravenous exposure to Fe2O3-NPs. However, iron level in plasma and iron content homeostasis in brain were disrupted after this exposure. Thus, our results demonstrated that Fe2O3-NPs could have transient effects on rat but the intravenous route is still safer that others which is encouraging for their use in medical and/or biological applications.

Several in vitro studies have convincingly demonstrated that SiO(2)NPs mediated cytotoxicity, which was dose-, time- and size-dependent. The data on in vivo toxicity of SiO(2)NPs are even more contradictory. In the present study, we investigated the effects of sub-acute exposure to SiO2-NPs on spatial learning and memory, the biochemical parameters and the histology of organs. Rats were injected intravenously with a single dose of SiO2-NPs (20 mg/kg) during five consecutive days. The analysis of spatial memory in the Morris water maze showed that SiO2-NPs disrupt the cognitive abilities of rats. Moreover, SiO2-NPs could changes the blood counts. However, biochemical markers remained unchanged. Histological examination showed that SiO2-NPs induced pathological changes in rat organs. In this finding NPs were shown to cause granuloma formation and inflammatory cells infiltration in the liver.

Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis. Rats were treated during seven consecutive days by intranasal instillations at a dose of 10 mg/kg body weight. The mean body weight increased significantly in IONP-exposed rats. Moreover, several hematological parameters were normal in treated rats except the platelet count which was increased. The biochemical study revealed that phosphatase alkaline level decreased in IONP-exposed rats, but no changes were observed for the other hepatic enzymes (ALT and AST) levels. The trace element homeostasis was slightly modulated by IONP exposure. Sub-acute intranasal exposure to IONPs increased dopamine and norepinephrine levels in rat brain; however, it did not affect the emotional behavior, the anxiety index, and the learning/memory capacities of rats.

Recently, the biosafety and potential influences of nanoparticles on central nervous system have received more attention. In the present study, we assessed the effect of aluminium oxide nanoparticles (Al2O3-NPs) on spatial cognition. Male Wistar rats were intravenously administered Al2O3-NP suspension (20 mg/kg body weight/day) for four consecutive days, after which they were assessed. The results indicated that Al2O3-NPs impaired spatial learning and memory ability. An increment in malondialdehyde levels with a concomitant decrease in superoxide dismutase activity confirmed the induction of oxidative stress in the hippocampus. Additionally, our findings showed that exposure to Al2O3-NPs resulted in decreased acetylcholinesterase activity in the hippocampus. Furthermore, Al2O3-NPs enhanced aluminium (Al) accumulation and disrupted mineral element homoeostasis in the hippocampus. However, they did not change the morphology of the hippocampus. Our results show a connection among oxidative stress, disruption of mineral element homoeostasis, and Al accumulation in the hippocampus, which leads to spatial memory deficit in rats treated with Al2O3-NPs.

Because of their whitening and photocatalytic effects, titanium dioxide nanoparticles (TiO2-NPs) are widely used in daily life. These NPs can be found in paints, plastics, papers, sunscreens, foods, medicines (pills), toothpastes, and cosmetics. However, the biological effect of TiO2-NPs on the human body, especially on the central nervous system, is still unclear. Many studies have demonstrated that the brain is one of the target organs in acute or chronic TiO2-NPs toxicity. The present study aimed to investigate the effect of TiO2-NPs at different concentrations (0.1 to 200 μg/mL) on murine microglial cells (BV-2) to assess their activity on cell growth and viability, as well as their neurotoxicity. Different parameters were measured: cell viability, cell proliferation and DNA content (SubG1 peak), mitochondrial depolarization, overproduction of reactive oxygen species (especially superoxide anions), and ultrastructural changes. Results showed that TiO2-NPs induced some cytotoxic effects with a slight inhibition of cell growth. Thus, at high concentrations, TiO2-NPs were not only able to inhibit cell adhesion but also enhanced cytoplasmic membrane permeability to propidium iodide associated with a loss of mitochondrial transmembrane potential and an overproduction of superoxide anions. No induction of apoptosis based on the presence of a SubG1 peak was detected. The microscopic observations also indicated that small groups of nanosized particles and micron-sized aggregates were engulfed by the BV-2 cells and sequestered as intracytoplasmic aggregates after 24-h exposure to TiO2-NPs. Altogether, our data show that the accumulation TiO2-NPs in microglial BV-2 cells favors mitochondrial dysfunctions and oxidative stress.

Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in many fields (paint, industry, medicine, additives in food colorants, and nutritional products). Over the past decade research, TiO2 NPs have been focused on the potential toxic effects of these useful materials. In the present study, we investigated the effects of subacute exposure to TiO2 NPs on emotional behavior in adult Wistar rats, the biochemical parameters, and the histology of organs. Animals were injected intraperitoneally (ip) with TiO2 NPs (20 mg/kg body weight) every 2 days for 20 days. The elevated plus-maze test showed that subacute TiO2 NPs treatment increased significantly the anxious index (AI) compared to control group. The toxicological parameters were assessed 24 h and 14 days after the last injection of TiO2 NPs. Subacute exposure to nanoparticles increased the AST/ALT enzyme ratio and LDH activity. However, the blood cell count remained unchanged, except the platelet count increase. Histological examination showed a little inflammation overall. Moreover, our results provide strong evidence that the TiO2 NPs can induce the liver pathological changes of rats. The intraperitoneal injection of TiO2 NPs increased the accumulation of titanium in the liver, lung, and the brain. The results suggest that TiO2 NPs could alter the neurobehavioral performance of adult Wistar rats and promotes alterations in hepatic tissues.

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain.

The aim of this study was to assess the potential subacute toxicity of zinc oxide (ZnO) nanoparticles (NPs) in Wistar rats in comparison with reference toxicant, zinc chloride (ZnCl2), of a non-nanoparticulate form. We therefore studied the relationships between zinc (Zn) accumulation, liver and kidney trace element levels, and plasmatic biochemical parameters. Rats in all groups were treated by intraperitoneal injection of ZnO NPs and/or ZnCl2 solution (25 mg/kg) every other day for 10 days. The contents of trace element in the liver and kidney were slightly modulated after ZnO NPs and/or ZnCl2 solution exposure. The same treatment increased the aspartate aminotransferase activity and uric acid concentration. However, ZnO NPs or ZnCl2 solution decreased the creatinine levels, whereas the combined intake of ZnO NPs and ZnCl2 decreased the glucose concentration. Interestingly, the analysis of the lyophilized powder of liver using the x-ray diffractometer showed the degradation of ZnO NPs in ZnO-treated group, instead there is a lack of NPs ZnO biosynthesis from the ZnCl2 solution injected in rats. These investigations suggest that combined injection of ZnO NPs and ZnCl2 solution has a possible toxic effect in rats. This effect could be related to Zn(2+) ion release and accumulation of this element in organs. Our findings provide crucial information that ZnO appeared to be absorbed in the organs in an ionic form rather than in a particulate form.