MgO and ZnO nanoparticles anti-nociceptive effect modulated by glutamate level and NMDA receptor expression in the hippocampus of stressed and non-stressed rats.

The anti-nociceptive mechanisms of MgO and ZnO nanoparticles have not been thoroughly investigated; in this study, we evaluated the effects of anti-nociceptive dose of MgO and ZnO NPs on glutamate level and NMDA receptor subunits expression (NR1, NR2 and NR2B) in the rat whole hippocampus with and without acute restraint stress. Adult rats were divided into control, MgO and ZnO NPs 5 mg/kg, the stress of 90 min alone and with MgO or ZnO NPs 5 mg/kg groups. All components injected intraperitoneally and the nociceptive response was measured with hot plate apparatus 90 min after injections or stress induction. Magnesium, zinc, glutamate levels and NMDA receptor subunits expression were measured in the animal hippocampus. MgO NPs, ZnO NPs and acute stress induced anti-nociceptive effect. MgO NPs observably decreased glutamate and increased magnesium levels and NR2B subunit expression. ZnO NPs decreased glutamate level. Stress elevated endogenous magnesium and zinc levels and also the NR2B expression, but did not change glutamate level. MgO and ZnO NPs in the presence of stress increased the glutamate level and ZnO NPs increased the zinc and the NR2A expression. Stress decreased endogenous magnesium in the hippocampus. MgO and ZnO NPs could affect pain perception by changing glutamate level in the whole hippocampus tissue, while ion level changes followed by injection could probably affect the gene expression in the presence and the absence of stress. It seems that stress indirectly could adverse nanoparticles effects on glutamate level and increase zinc ion releasing from ZnO NPs by activating the gene expression without affecting pain perception.

Cognitive and hippocampus biochemical changes following sleep deprivation in the adult male rat.

Sleep deprivation (SD) influences physiological processes such as cognitive function. The balance of oxidant and antioxidant markers, neurotrophic factors and magnesium are affected by sleep deprivation but there is no difference between pre and post training sleep deprivation. This study was designed to investigate memory retrieval and biochemical factors such as oxidant and antioxidant enzyme, brain-derived neurotrophic factor (BDNF) and magnesium levels in the hippocampus following pre and post-training sleep deprivation. Male Wistar rats (weighing 200 ±â€¯20 g) in below groups were used: control 1, 24, 48 and 72 h SD before training groups, control2, 24 h SD1 after training (being evaluated 24 h after training) and SD2 24 after training (being evaluated 48 h after training). Memory was evaluated 90 min, 24 h or 48 h after training by step-through passive avoidance apparatus. Multiple platforms method was used to induce SD. Oxidant and antioxidant markers including glutathione (GSH), glutathione reductase (GPx), malonedialdehyde (MDA), Total antioxidant concentration, catalase, superoxide dismutase (SOD), magnesium and BDNF were assessed in the hippocampus or/and brain. 72 h pre-training SD impaired short and long-term memory significantly. There was no significant difference in hippocampus oxidant and antioxidant markers compared to control. Hippocampal BDNF and magnesium did not show any changes in all SD groups. Lack of correlation between memory impairment and levels of BDNF, magnesium and/or oxidant and antioxidant balance in the hippocampus is likely to be related to animal locomotor activity in the multiple platforms method. More research is needed to clarify the role of neurochemical systems.

Neurobehavioral and biochemical modulation following administration of MgO and ZnO nanoparticles in the presence and absence of acute stress.

In this work, the effects of MgO and ZnO nanoparticles were investigated on some behavioral, hormonal and biochemical changes following acute stress. Wistar male rats were divided into groups of control, different times of restraint stress (90, 180 and 360 min), nano-MgO or nano-ZnO alone and with acute restraint stress. Anxiety-like behaviors and pain perception were evaluated by elevated plus maze and hot plate apparatus respectively. Levels of corticosterone hormone, malondialdehyde (MDA) and catalase activity, Mg, Zn, Fe and Ca were evaluated in the serum and hippocampus. The results showed that nano-MgO and nano-ZnO improved anxiety induced by restraint stress and reduced locomotor activity significantly at high doses, while at low doses could induce analgesia in the non-restraint group. Corticosterone level increased temporarily in the presence of 360 min stress while it was reduced in the stress of 90 min just 2 h after stress induction. The highest dose of nano-MgO increased the corticosterone level in non-restraint animals while nano-ZnO reduced it in all the groups. The 90 min stress was increased MDA level and nanoparticles decreased catalase activity in the hippocampus significantly. Influences of both nanoparticles on levels of Mg, Zn, Fe and Ca in the serum and hippocampus seem to be more visible than the other measured biochemical factors. Accordingly, in acute stress conditions, low doses of nano-MgO and nano-ZnO had suitable effects on behavioral responses. It seems that these effects were mostly through the central and peripheral changes of mentioned element's content and acute stress could increase nanoparticles toxicity.

Interaction between Analgesic Effect of Nano and Conventional size of Zinc Oxide and Opioidergic System Activity in Animal Model of Acute Pain.

INTRODUCTION: Today Nano-medicine tries to produce new drugs to reduce the dosage and side effects of their conventional forms. According to the interaction between zinc and opioidergic system activity, this study has investigated the effect of new kind of zinc supplement, nano zinc oxide (nZnO), in compared to its conventional form (cZnO), in presence and absence of opioidergic system activity on acute pain. METHODS: Adult male Wistar rats (weighting 200±20gr) divided into groups: control (receiving saline %0.9), nZnO (1, 5, 10, 20 mg/kg), cZnO (1, 5, 10, 20 mg/kg), naloxone 1mg/kg, morphine 6 mg/kg, and co-injected groups of morphine and/or naloxone with nZnO (5mg/kg) and/or cZnO 10 mg/kg. Hot plate assay was used to evaluation of nociception and post injected latencies were recorded every 30 min for 90 min after I.P. injections of drugs. In co-injected groups latency time recorded after 60 minutes. RESULTS: Data indicated that both of ZnO supplements reduced latency time in dose and time dependent on the effect of nZnO was higher than cZnO. Also these components could improve anti-nociception effect of morphine and naloxone could not change the effect of these supplements. DISCUSSION: It seems that nZnO has more efficacy than its conventional form to showing analgesic effect that probably is related to the physicochemical properties of nZnO. Also may be these supplements have interaction with opioideric system in body.

Effect of Intra CA1 and Intraperitoneal Administration of Opioid Receptor Modulating Agents on The Anxiolytic Properties of Nano and Conventional ZnO in Male Rats.

OBJECTIVE: Nano components are today's new wonder material. However, the safety or toxicity of these components in humans is not yet clear. In a previous study we indicated that nano ZnO (nZnO) has a stronger anxiolytic effect compared to the conventional ZnO (cZnO). The present study was designed to evaluate the intraperitoneal administration of an opioidergic receptor agonist and antagonist of as well as the intra CA1 administration of an opioidergic receptor antagonist on the anxiolytic properties of nano and conventional ZnO in adult male Wistar rats. MATERIALS AND METHODS: In this experimental study, rats received drugs via two modes of injection; intraperitoneal (IP.) and intra CA1 (intra hippocampus, CA1 area). Firstly, nZnO (5, 10, 20 mg/kg), cZnO (5, 10, 20 mg/kg), morphine 6 mg/kg, and naloxone 1 mg/kg were injected IP and naloxone 1µg/rat was injected intra CA1. Subsequently, morphine and na- loxone (IP and intra CA1) were co-injected with the effective dose of nZnO and cZnO. An elevated plus maze was used to evaluate anxiety related behavior and anxiety parameters 30 minutes after the second injection. RESULTS: The results indicated that the anxiolytic effects of nZnO 5 mg/kg and cZnO 10 mg/kg were equal. When injected intraperitoneally, naloxone increased anxiety but did not inhibit the anxiolytic effect of nZnO and cZnO. The anxiolytic effects of morphine potentiated the anxio- lytic effects of ZnO, particularly nZno. When introduced via intra CA1 injection naloxone alone had no effect on anxiety behaviors and did not inhibit the anxiolytic effect of nZnO. CONCLUSION: It seems that the opioidergic system activity involved in the anxiolytic effect of nano and conventional ZnO may operate through shared and unshared pathways.

Effects of nano and conventional zinc oxide on anxiety-like behavior in male rats.

OBJECTIVES: Current drug therapies for psychological disorders, such as anxiety, are not as effective as expected, and it has been shown that zinc supplements, such as zinc oxide (ZnO), can influence anxiety. ZnO nanoparticles (ZnO NPs) are among the most used nanomaterials produced and applied in many products. MATERIALS AND METHODS: This study investigated the effects of ZnO NPs in comparison with conventional ZnO (cZnO) on anxiety-like behaviors. Adult male Wistar rats were divided into groups: Control (receiving saline 0.9%), ZnO NPs (5, 10, 20 mg/kg), and cZnO (5, 10, 20 mg/kg). All drugs were dispersed in saline 0.9%, and 30 minutes after intraperitoneal (i.p.) injection of drugs, elevated plus maze apparatus was used to evaluate anxiety. RESULTS: ZnO NPs (5 mg/kg) and cZnO (10 and 20 mg/kg) significantly increased the percentage of time spent in open arm (open arm time % OAT) compared with the control group (P < 0.05). This indicates the anxiolytic effect of such components; in addition, ZnO NPs (20 mg/kg) reduced locomotor activity (P < 0.05). Serum zinc concentration increased by both anxiolytic dose of components (from 1.75 ± 1.07 (mg/l) in control group to 5.31 ± 0.53 (mg/l) in ZnO NPs (5 mg/kg) and 10.38 ± 0.90 (mg/l) in cZnO (10 mg/kg) groups). Also, all doses increased serum pH (from 7.3 ± 0.05 in control group to 8.1 ± 0.05 in ZnO NPs (5 mg/kg) and 8.05 ± 0.01 in cZnO (10 mg/kg) groups and kept them constant after 24 hours. CONCLUSION: Results indicate that the anxiolytic effect of ZnO NPs is much higher than its conventional form, but the introduction of ZnO NPs, as a new drug for treatment of anxiety disorder, needs further investigations.