فهرست مطالب

Physiology and Pharmacology - Volume:23 Issue: 4, 2019
  • Volume:23 Issue: 4, 2019
  • تاریخ انتشار: 1398/09/10
  • تعداد عناوین: 11
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  • Alireza Gharib, Amir Shojaie, Meysam Zare, Alireza Komaki, Abdolrahman Sarihi* Pages 235-248

    Epilepsy is a common neurological disorder that affects approximately 50 million people and about 30% of them have seizures despite antiepileptic-drug therapy. Even if 50% of these 600,000 or so patients benefit from surgical resection, many would still need new therapeutic approaches. Deep brain stimulation (DBS) has been suggested as an alternative to drug therapy. Low frequency stimulation (LFS) is an effective pattern of DBS that can decrease epileptic seizures. The incidence of epileptic seizures has been described by an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmission. This phenomenon may be affected by other neurotransmitter systems, including serotonin (5-hydroxytryptamine, 5-HT). The Serotonergic system undergoes many alterations in the epileptic brain. The link between LFS and serotonin release has been studied and it is documented that 5- HT1A receptor antagonist reduces the anti-convulsant effects of LFS. Thus, considering the effects of the serotonergic system in neuronal activities in the epileptic brain, it may be involved in the anti-convulsant mechanism(s) of LFS. In this review, we introduce the effects of low frequency stimulation on seizure and its possible mechanisms. The role of some neuromodulators in mediating the anti-convulsive effects of LFS and the probable signaling changes will be discussed.

    Keywords: Epilepsy, Low frequency stimulation, Neuromodulator
  • Keivan Lorian, Mehri Kadkhodaee, Farzaneh Kianian, Arash Abdi, Hamidreza Sadeghipour, Behjat Seifi* Pages 249-260

    Varicocele is defined as the non-palpable enlargement of the spermatic venous plexus, which has implications on the sperm quality and fertility. The guidelines for managing varicocele in adolescents are not fully determined yet. However, based on the recent reports, during varicocele injuries to testicular tissues may be a result of the formation of reactive oxygen species (ROS) and the subsequent oxidative damage. The testis has a high metabolism rate and cell replication which itself causes excessive production of the ROS and decreases antioxidant capacity. Massive generation of ROS and their interaction with lipids, proteins and nucleic acids has adverse effects on the normal cell function. This review article describes the varicocele, its etiology, pathophysiological mechanisms and current treatment methods. An electronic search has been conducted, during 2018, via PubMed and Medline database English literature. Peer-reviewed articles were targeted and the following key-words were used: varicocele, diagnosis, etiology, cellular and molecular mechanisms. Available full-text articles were read. Related articles were also scrutinized. A hand search was also driven. Taken together, this review article mention three main pathophysiology of varicocele that can be treated by natural antioxidant. In addition, hydrogen sulfide as another factor was discussed because the reduction of this substance contribute to the male infertility which induce by varicocele.

    Keywords: Varicocele, Diagnosis, Etiology, Cellular, molecular mechanisms
  • Mojtaba Keshavarz*, Atena Amiri Pages 261-269
    Introduction

    Astrocyte, S100B and nitric oxide may have a role in the pathogenesis and treatment of epilepsy. However, the effects of nitric oxide and S100B on the gliotoxic effects of chemical convulsants such as pentylenetetrazole (PTZ) is unknown. Therefore, we aimed to evaluate the effects of S100B and nitric oxide on gliotoxicity of PTZ in a 1321NI1 astrocytic culture.

    Methods

    The 1321N1 astrocytes were exposed to PTZ (40mM), arundic acid (50μM) or both of them for 24h. In addition, we poured L-arginine (100 or 500μM), N-nitro-L-arginine methyl ester (100 or 500μM), 7-nitroindazole (30 or 100μM) and aminoguanidine (50 or 100μM) to the culture media contained PTZ, arundic acid or both of them and incubated for 24h. Cell viability was measured by the methylthiazolyldiphenyl-tetrazolium bromide reagent and the S100B protein level was measured using an enzyme-linked immunosorbent assay.

    Results

    There was a negative correlation between cell viability in astrocytes and the intracellular S100B levels. PTZ decreased cell viability, but it increased the intracellular S100B levels. Arundic acid, N-nitroarginine methyl ester, 7-nitroindazole and aminoguanidine reversed the PTZ effects on cell viability and intracellular S100B levels. Adding the L-arginine to PTZ plus arundic acid reduced the modulatory effects of arundic acid on PTZ.

    Conclusion

    Nitric oxide and S100B have a role in gliotoxicity of PTZ in cell culture. Arundic acid suppresses PTZ-induced S100B elevation and gliotoxicity possibly by modulation of the nitric oxide pathway.

    Keywords: Arundic acid, Astrocytes, Nitric oxide, Pentylenetetrazole, S100 Calcium Binding Protein beta Subunit
  • Amin Abdollahzade Fard, Ehsan Saboory*, Yaghob Tahmazi, Yousef Rasmi Pages 270-278
    Introduction

    Pre-gestational nutrition, before and during pregnancy, might play a key role in nervous system. This study aimed to investigate effect of pre-gestational administration of thymoquinone (TQ) on pentylenetetrazole (PTZ)-induced seizure in rat offspring.

    Methods

    Thirty-two female Wistar rats were divided to four groups (n=8) as follows: 1-control (received one ml ethanol 25% by gavage for seven constitutive days), 2-TQ10, 3-TQ 40 and 4-TQ 80. The rats in the groups 2, 3 and 4 received 10, 40 and 80mg/kg TQ dissolved in one ml ethanol 25% by gavage for seven constitutive days, respectively. The day after finishing the TQ administration, each female rat was mated with a sexually experienced male rat. The pregnant rats were housed in groups of four per cage until the day 20 of gestation. Then, the rats were individually transferred to a separate cage and the same conditions were applied for all of them. After parturition, the pups were counted, weighed and culled to eight in each litter. On postnatal day 14 (P14) and P21, the pups were subjected to PTZ-induced seizure.

    Results

    Latency of the first seizure decreased in the TQ40 and TQ80 groups and the duration of focal seizure increased both at P14 and P21. The progress of seizure stages and duration of tonic-clonic seizures were suppressed in TQ-treated rats.

    Conclusion

    Exposure to TQ before conception potentiates focal seizure while suppresses generalized PTZ-induced seizure in rat offspring. TQ significantly changed the PTZ-induced seizure pattern in favor of focal seizure.

    Keywords: Thymoquinone, Seizure, Pentylenetetrazole, Pre-gestation
  • Moslem Riyahi, Mahnaz Taherianfard* Pages 279-285
    Introduction

    Parkinson’s disease (PD) is a neurodegenerative disorder with progressive degeneration of dopaminergic neurons in the nigrostriatal system. Toxoplasma gondii (TG) is a parasite that has gene for tyrosine hydroxylase and can produce dopamine. It is not clear whether TG infection has an effect on PD and its motor defect or not. The aim of the present study was to investigate the effects of 6-hydroxydopamine (6-OHDA) model of PD on motor defects, striatal dopamine and brain-derived neurotrophic factor (BDNF) levels in pre-infected TG rats.

    Methods

    Fifty Sprague-Dawley adult male rats weighing 200-300g were used in five groups. Induction of PD were done by unilateral intra-striatal injection of 6-OHDA, and to prove PD induction the animals were tested for drug-free elevated body swing behavior and bar test. Dopamine and BDNF concentration in striatum were measured by ELISA kits. Giemsa staining of brain smears confirmed TG infection.

    Results

    The results showed that TG infection prior to PD induction attenuated the elevated body swing bias and the latency in movement on the bar compared to PD rats without infection. The levels of striatal dopamine and the BDNF in TG infected PD rats was significantly higher than the PD rats without infection.

    Conclusion

    Motor defects in experimental 6-OHDA- induced PD rats can be improved by pre-infection with TG through the increased levels of striatal dopamine and BDNF.

    Keywords: Parkinson’s disease, Toxoplasma gondii, BDNF, Dopamine
  • Manizheh Gholami, Ziba Rajaei*, Maryam Malek Pages 286-295
    Introduction

    Peripheral administration of lipopolysaccharide (LPS), can cause production of cytokines in the brain and subsequently impair learning and memory function. Carvacrol is a phenolic monoterpene that is found in the essential oils of the Lamiaceae family. Anti-inflammatory and antioxidant activities of carvacrol have been demonstrated in previous studies. The aim of the current study was to evaluate the effects of carvacrol on spatial learning performances in LPS-treated rats.

    Methods

    Male Wistar rats were pretreated with carvacrol at doses of 10, 25 and 50mg/kg for a week. Then, the animals received LPS injection (1mg/kg, ip) and treatments continued for 3 more weeks. Spatial learning performances were assessed in rats by the Morris water maze from post-injection days 18 to 21. Biochemical assays (interleukine-1β, lipid peroxidation and total thiol levels) were performed in the hippocampus and cerebral cortex at the end of the experiment.

    Results

    LPS-treated rats displayed higher escape latency and longer traveled distance as compared to control rats. In addition, chronic treatment of LPS-treated rats with carvacrol at a dose of 25mg/kg significantly decreased escape latency and traveled distance as compared to untreated-LPS rats. Biochemical assessments showed no significant difference in inflammatory and oxidative stress markers levels among the groups.

    Conclusion

    Our findings demonstrated that chronic treatment with carvacrol improves spatial learning performances in LPS-treated rats. This might be due to antioxidant, anti-inflammatory and anticholinesterase activities of carvacrol in early LPS challenge.

    Keywords: Carvacrol, Lipopolysaccharide, Spatial learning, Cytokines, Oxidative stress, Inflammation
  • Sara Soleimani Asl, Marek J. Łos, Mehdi Mehdizadeh* Pages 296-301
    Introduction

    Given that pelargonidin is an anthocyanin that exhibits neuroprotective effects and Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) and cognitive dysfunction subsequently, herein, we examined the effects of pelargonidin on Aβ-induced long-term potentiation deficits in rats.

    Methods

    AD was induced using intrahippocampal injections of the Aβ in the adult Wistar male rats. The rats received single intraperitoneal injections of pelargonidin (3mg/kg). Long-term potentiation in the perforant path- dentate gyrus synapses was assessed electrophysiologically by measuring the field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude.

    Results

    Our results showed that Aβ significantly decreased fEPSP slope and SP amplitude in comparison with the control and sham groups, whereas pelargonidin increased these parameters in comparison to the Aβ group.

    Conclusion

    It is probably that pelargonidin could improve Aβ-induced cognition deficit in rats.

    Keywords: Amyloid β-peptide, Pelargonidin, Long- term potentiation, Hippocampus
  • Mohamad Hallak, Hakan Balci, Caner Günaydın, S. Sirri Bilge* Pages 302-308
    Introduction

    Pregabalin (PGB) is an analog of gamma-aminobutyric acid (GABA) with antinociceptive, antihyperalgesic and antiallodynic properties which frequently used in clinical pain management. Effect of PBG in neuropathic pain, incisional-inflammatory injury, post-operational pain, chronic pain and experimental pain models have already shown. It has been already known that muscarinic and serotonergic-2A receptors have a role in pain transmission.

    Methods

    in this study, role of muscarinic and serotonergic-2A receptors in antinociceptive effect of pregabalin were evaluated with hot-plate and tail flick tests and effects of administered drugs on locomotor activity were measured with automated activity cage.

    Results

    PGB treatment (30 and 100mg/kg) caused longer latency in hot plate and tail flick tests than saline group. That antinociceptive effect of pregabalin abolished by ketanserin (1mg/kg) and atropine (1mg/kg) treatment.

    Conclusion

    However, there is lack of knowledge about role of nociceptive pathways underlying pregabalin mediated antinociception. Our results suggest that cholinergic and serotonergic systems have a role in antinociceptive effect of PGB which has seen in these somatic pain tests.

    Keywords: Pregabalin, Somatic pain, Ketanserin, Atropine
  • Alexandre Kormanovski, Maria Del Carmen Castillo Hernández*, Gustavo Guevara Balcázar, Teresa Pérez, Eleazar Lara Padilla Pages 309-321
    Introduction

    The aim of this study was to evaluate gender differences in the oxidant/antioxidant response in different tissues of trained mice during physical stress with the hyperbaric oxygen preconditioning (HBOP) beforehand.

    Methods

    Trained mice of both genders treated by HBOP were divided into three groups including basal, fasting and prolonged exercise. Parameters of oxidant/antioxidant state including nitric oxide (NO) were measured in blood and tissues. Gender differences in the effects of HBOP were analyzed in the basal levels, fasting and in the net response to exercise.

    Results

    HBOP diminished the elevated basal levels of lipoperoxidation, NO, antioxidant enzymes and glutathione in liver of females only, compared to untreated group. A similar decrease in the basal levels of NO and enzymes was observed in other tissues of females as well. A strong decrease of basal level of glutathione in liver coincided to its increase in muscle, brain, small intestine and adipose tissue. Therefore, females after HBOP started prolonged exercise with a lower basal level of oxidative stress and antioxidant defense in liver but increased basal levels of glutathione in most tissues. Consequently, during exercise, females showed a strong net response in the liver and stability in muscle tissue, while in males the contrary response was found.

    Conclusion

    Only in the tissues of females did HBOP drastically affect the basal levels of the oxidant/antioxidant status. Although performance decreased in both genders, it was better in females, likely related to the redistribution of glutathione from the liver to other tissues after HBOP.

    Keywords: Gender difference, Oxidative stress, Antioxidant, Nitric oxide, Hyperbaric oxygen
  • Nibras H. Abdulsada Al Ghuraibawi*, Zahraa Al Mudhafer, Salam J. Mohammed Pages 322-329
    Introduction

    Diabetes mellitus may be associated with many complications including diabetic nephropathy and pulmonary impairment, the pathogenesis and progression of these complications may be related to oxidative stress. Bilirubin, which is a non-polar molecule have antioxidant properties. The relationship between occurrence, development and prognosis of diabetic complications and bilirubin concentration had become a research focus. However, no study has evaluated the relationship between protective effect of bilirubin on both diabetic nephropathy and pulmonary impairment in type II diabetic patients.

    Methods

    The design of the study is a cross sectional study included 245 type II diabetic patients. Spirometry was done for all patients. Albumin/creatinine ratio (ACR), glycosylated hemoglobin, total serum bilirubin and serum glutathione reductase enzyme were measured.

    Results

    There was a significant statistical negative relationship between serum bilirubin and glutathione reductase enzyme with ACR and significant statistical positive relationship between serum bilirubin and glutathione reductase enzyme with lung function parameters (forced expiratory volume in the first second and forced vital capacity).

    Conclusion

    serum bilirubin levels had a protective effect against diabetic nephropathy and impairment of pulmonary function. If serum bilirubin levels were moderately high but within the normal range, this was related with decreased risk of diabetic complications and there was a parallel relationship between serum bilirubin levels and the glutathione reductase enzyme levels in type II diabetic patients.

    Keywords: Bilirubin, Diabetes mellitus type II, Diabetic nephropathy, Pulmonary impairment, Oxidative stress
  • Roxana Soukhaklari, Rasoul Ghasemi, Maryam Moosavi* Page 330
    Introduction

    Human neuroblastoma cell line is used in studying Parkinson’s disease (PD) due to its similarities to dopaminergic neurons. 6-hydroxydopamine (6-OHDA), a catecholaminergic neurotoxin, has been widely used to induce cell death in cellular models of PD. Although the brain glucose entry is not dependent on insulin, this peptide has been reported to have a role in PD, in which insulin signaling disruption is reported. This study aimed to evaluate, if insulin is efficient in preventing 6-OHDA induced cell death in human neuroblastoma cells as well as its effect on phoshorylated Akt (p-Akt)/total Akt (t-Akt) ratio.

    Methods

    The cells -grown in DMEM/F12 media supplemented with 10% fetal bovine serum- were exposed to 6-OHDA with/without insulin for 24h, and then MTT assay was done to examine their viability. A pilot study was performed to assess the protective doses of insulin and accordingly the doses 0.9 and 1mM were selected. Western blot assay was done to evaluate the effect of 6-OHDA or insulin on p-Akt and t-Akt level.

    Results

    The results indicated that insulin has potency to prevent SH-SY5Y cell death, and p-Akt/t-Akt decline induced by 6-OHDA.

    Conclusion

    The results suggested insulin as a protective agent in dopaminergic
    cells.

    Keywords: Insulin, Parkinson’s disease, 6-OHDA, SH-SY5Y, Akt