IRANIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Year:2019 | Volume:3 | Issue:3 (11)|Papers Count:8

Background and aims: In the previous study, the effects of Zataria multiflora (ZM) and its main constituents carvacrol and thymol were evaluated and it was found that they could alleviate cognitive impairments caused by amyloid β (Aβ ) in rodent model of Alzheimer’ s disease. In this study, the effect of ZM against Aβ 25-35-induced cytotoxicity and reactive oxygen species (ROS) accumulation in PC12 cells as a model of Alzheimer's disease was evaluated. Methods: First, PC12 cells were exposed to Aβ 25-35 and different concentrations of ZM for 48 h. Then, the cell viability was determined by methyl thiazolyl tetrazolium (MTT) method. Fluorospectrometer was employed to observe ROS production. Results: The results indicated that concentrations of 18. 75, 37. 5 and 75 μ l/L of ZM could significantly rescue and protect PC12 cells against Aβ 25-35-induced cytotoxicity (p< 0. 001). Furthermore, the data demonstrate that Aβ 25-35 induced intracellular ROS, while the concentrations of 18. 75 (p <0. 05), 37. 5 and 75 (p <0. 001) μ L of ZM could significantly reverse Aβ 25-35 induction of ROS generation. Conclusion: According to these findings, ZM could attenuate the level of intracellular ROS induced by Aβ . Therefore, ZM could have antioxidant activity. Ability of ZM to reduce ROS and its protective effects against Aβ-induced cellular damage in PC12 cells may indicate its potential for treatment of Alzheimer’ s disease. Further studies are required to determine its clinical efficacy.

Background and aims: In this study, the toxicity and carcinogenicity of an organophosphate pesticide, diazinon, were studied in the mouse by MTT, micronucleus and karyotype methods. Morphological changes of cell lines in the vicinity of diazinon were also evaluated and recorded. Methods: Mice were randomly divided into two groups (n=15 per group): treatment and control groups. In the treatment group, diazinon (1 ml of 1 ppm concentration) was applied once daily topically on the shaved skin and for 12 weeks; in the controls, physiological salt solution was used. At the end of the period, tissue samples were taken from the organs after autopsy. Murine L929 fibroblast cells were cultured with and without diazinon (10, 25, 50, 100 μ g/ml). The morphological changes of the cells were evaluated after 48 hours. The cytotoxicity was assessed in vitro by MTT assay and micronucleus and karyotype and IC50 percent were also determined. Results: Microscopic observations of kidney tissue revealed mild cytotoxicity in proximal tubules. Mild hepatotoxicity was also observed in the liver tissue. Morphological results of cell line showed that diazinon (50 μ g/ml) had a significant effect compared to the control group. The percentage of micronucleus in the group treated with 100 μ g/ml of diazinon was significantly higher than the control. In the MTT assay, the mean optical absorption at concentrations of 10, 25, 50, 100 μ g/ml was significantly different from that of the control group (P <0. 05). Conclusion: Skin contact with Diazinon induces pathologic effects on organs, cytotoxicity, and procarcinogenic effect in mice.

Background and aims: The anxiolytic effect of magnesium oxide nanoparticles has been determined, but its effect on the reduction of anxiety caused by cyclophosphamide is unknown. The aim of this study was to evaluate the effect of magnesium oxide nanoparticles on the anxiety resulted from cyclophosphamide and interaction of cholinergic muscarinic receptor activity with it in the adult male mice. Methods: In this experimental study, 84 adult male NMRI mice (25-35 g) were divided into 12 (n=7) groups including: control (saline, 5 ml/kg), magnesium oxide nanoparticles (2. 5 and 5 mg/kg), cyclophosphamide (50 mg/kg), magnesium oxide nanoparticles 2. 5 or 5 mg/kg with cyclophosphamide 50, scopolamine (1mg/kg), scopolamine 1 with magnesium oxide nanoparticles 2. 5 or 5 mg/kg, scopolamine 1 with cyclophosphamide 50, scopolamine 1 and magnesium oxide nanoparticles 2. 5 or 5 mg/kg and cyclophosphamide 50. All drugs were injected intraperitoneally and anxiety and motor activity of animals were evaluated by the elevated plus maze apparatus. Results: Magnesium oxide nanoparticles (2. 5 and 5) prevented the anxiety of cyclophosphamide (50), while it has no effect on motor activity. The anxiolytic effect of magnesium oxide nanoparticle was reduced in the presence of scopolamine. The effect of cyclophosphamide induced anxiety was reduced in the presence of scopolamine. The preventive effect of magnesium oxide nanoparticle on the anxiety of cyclophosphamide was reduced in the presence of scopolamine. Conclusion: It seems that cholinergic muscarinic receptors interfere in the anxiolytic effect of magnesium oxide nanoparticle alone and in combination with cyclophosphamide.

Background and aims: Evidence report a bidirectional relationship between sleep deprivation (SD) and anxiety. Although many studies have confirmed the beneficial effects of alpha-lipoic acid (ALA) on central nervous system diseases, its effect on anxiogenic behaviors in SD condition has not been investigated. This study examines the effect of ALA on anxiety-related behaviors in SD rats. Methods: Male Wistar rats were sleep deprived in the water box for 24 h, and then submitted to the elevated plus maze (EPM) for assessing the anxiety-related behaviors. Blood samples were obtained to assess the serum corticosterone level. Results: SD rats decreased the percentage time spent in the open arms (%OAT), showing an anxiogenic-like behavior. Pretreatment administration of ALA (35 mg/kg, three times, once in each day) prevented the anxiogenic-like behavior in the SD rats, suggesting the inhibiting effect of ALA on the anxiogenic response induced by SD. Moreover, ALA alone had no effect on the EPM parameters. Meanwhile, in none of the groups the open arm entry and locomotion altered compared to the control group. In addition, ALA prevented the increased corticosterone level in the blood of SD rats. Conclusion: The results suggest that SD causes an anxiogenic-like behavior and increases corticosterone level. Pretreatment with ALA prevents the anxiogenic-like effects and decreased the corticosterone level in SD rats. Given the beneficial effect of ALA on improving the performance of rats in anxiety-related behavior in SD conditions, this compound might be future chance in order to decrease the disrupting effects of SD.

Background and aims: Inflammatory cytokines and oxidative stress play an important role in the pathogenesis of non-bacterial chronic prostatitis. Given the role of vitamin D3 in balancing inflammatory and anti-inflammatory cytokines and having antioxidant properties, this study aimed to evaluate the effect of vitamin D3 on biochemical, histopathological and oxidative changes in Wistar male rats induced by chronic non-bacterial prostatitis (CNP). Methods: Twenty four adult male Wistar rats were divided into healthy, CNP without treatment, and two treatment groups including CNP + cernilton and CNP + D3 groups. CNP was induced by single intraprostatic injection of 3% carrageenan. Rats received orally cernilton 100 mg/kg and Vitamin D3 5μ g/kg one week after CNP induction for 21 days. Prostatic index (PI), Oxidative index (OI), blood urea nitrogen (BUN), creatinine, calcium and histopathological changes were compared between groups. Results: Oral administration of cernilton and Vitamin D3 in the treatment groups significantly (p < 0. 05) decreased prostatic and oxidative stress indices and serum creatinine compared to the untreated group. Vitamin D3 significantly increased (p < 0. 05) serum calcium concentration compared to the untreated group. No significant differences were observed between the treatment groups and the untreated group in the blood urea nitrogen concentration. In a quantitative evaluation of histopathological results, a significant decrease in mean cell wall hyperplasia, inflammation, and total hyperplasia and inflammation was observed in the vitamin D3 treated group compared to the untreated group. Conclusion: Our study indicates that Vitamin D3 shows protective effects on CNP induced by carrageenan in rats due to its antioxidant and anti-inflammatory properties.

Background and aims: Traumatic brain injury (TBI) is considered as one of the most common neurologic disorders after stroke and Alzheimer's disease. Understanding the pathogenesis of TBI helps to discover new treatment strategies. Neuroinflammation is the main feature of TBI. We aimed to measure expression level of tumor necrosis factor-α (TNF-α ), one of the main factor of neuroinflammation, in the rat brain at different times after induction of TBI. Methods: TBI was exerted to adult male rats under anesthesia by controlled cortical compact (CCI) model. Trauma was exerted to parieto-occipital cortex by 4. 5 m/s speed. TBI was confirmed by staining the injured area. TNF-α level was measured in the injured brain region semiquantitatively by western blot technique at 0, 3h. 6h, 24h, and 5 days after TBI. Results: TBI induced an injury with 2mm depth in the parieto-occipital cortex. Compared to control and shamoperated rats, TNF-α level significantly increased in the injured brain area 3h and 6h after TBI (p < 0. 01). Conclusion: TNF-α level increases considerably in rat brain during the first hours after TBI in CCI model. This data is useful in designing the pharmacologic or non-pharmacologic protocols for preventing TBI-induced neuroinflammation.

Background and aims: The transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors play a substantial role in pain transmission and the receptor antagonist capsazepine could alleviate pain in various pharmacological models. On the other hand, the enzyme cyclooxygenase type 2 (COX-2) has been shown to exist in central nervous system, particularly in hippocampal glutamatergic neurons as well as in cortex and the enzyme inhibition could alleviate pain transmission and perception. The aim of the present study was to investigate the analgesic effect of capsazepine and its possible interaction with COX-2 inhibition in the brain. Methods: Male wistar rats (200– 250 g) were used in this study. One week after insertion of a stainless steel guide cannula by stereotaxic surgery, drugs were administered into left lateral ventricle on the day of experiment 10 min before formalin test and the pain related behavior of the rat was measured based on method described by Dubuisson and Dennis. Experimental groups consisted of capsazepine (5 and 50 nM), celecoxib (2 and 20 nM), and co-administration of capsazepine (5 nM) and celecoxib (2 nM). Results: Results showed a significant decrease in pain related behavior in rats received capsazepine 5 nM (92. 4 ± 1. 1), capsazepine 50 nM (57. 0 ± 2. 1), celecoxib 2 nM (83. 9 ± 1. 1), or celecoxib 20 nM (51. 6 ± 1. 4) compared with the control (103. 60 ± 2. 0) group. Moreover, co-administration of celecoxib (2 nM) and capsazepine (5 nM) significantly decreased pain related behavior of rats (50. 6 ± 0. 8) compared with the group received celecoxib (2 nM) or capsazepine (5 nM) alone, respectively. Conclusion: The results suggest a possible additive and/or synergistic interaction between celecoxib and capsazepine in analgesic effects in formalin test.

Background and aims: RFamide-related Peptide-3 (RFRP-3) belongs to the RFamide family which plays a key role in appetite regulation by stimulation of NPFF receptor in vertebrates. The present study aimed to investigate the effects of NPFF receptor on feeding behavior and its interaction with melanocortin systems in neonatal chickens. Methods: Two hundred and Twenty neonatal male broiler-type (ROSS 308) chickens were divided randomly into 5 experimental groups. Each experiment had a control group and three treatment groups (n=11). Cumulative food intake was recorded and analyzed in five-day-old chicks, after intracerebroventricular injection at 30, 60 and 120 minutes after injection. Results: Injection of MC3R receptor agonist (γ 1-MSH; 5, 10 pmol) and MC4R receptor agonist (PG-931; 25, 50 pmol) decreased food intake (p ˂ 0. 05). However, injection of 8 and 16 nmol of NPFF receptor antagonist (RF9) increased food intake in neonatal chicks in all time-points (p ˂ 0. 05). Co-injection of RF9 and γ 1-MSH showed no significant alteration on hypophagic effect induced by γ 1-MSH (p ≥ 0. 05). Yet, co-injection of RF9 and PG-931attenuated the hypophagic effect of PG-931 in all time-points (p ˂ 0. 05). Conclusion: The results of the present study indicate that the hypophagic effect of MC4R in neonatal male broilertype (ROSS 308) chickens may be mediated by NPFF receptor.