@article{ author = {Shojaei, Amir and Semnanian, Saeed and Janahmadi, Mahyar and Moradi, Homeira and Firoozabadi, Seyad Mohammad and Mirnajafi-Zadeh, Jav}, title = {Effect of repeated transcranial magnetic stimulation during epileptogenesis on spontaneous activity of hippocampal CA1 pyramidal neurons in rats}, abstract ={Introduction: Considering the antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS), the effect of rTMS applied during amygdala kindling on spontaneous activity of hippocampal CA1 pyramidal neurons was investigated. Materials and Methods: A tripolar electrode was inserted in basolateral amygdala of Male Wistar rats. After a recovery period, animals received daily kindling stimulations until they reached stage 5 seizure. In one group of animals, rTMS at frequency of 1 Hz were applied to hippocampus once daily at 5 min after termination of kindling stimulations. 24 h after the last kindling stimulation, spontaneous activity of CA1 pyramidal neurons of the hippocampus was investigated using whole cell patch clamp technique. Results: Kindling-induced seizures resulted in increment of spontaneous activity of hippocampal CA1 neurons, but application of rTMS during amygdala kindling prevented it. Moreover, rTMS administration inhibited the kindling-induced enhancement of afterdepolarization (ADP) amplitude and action potential duration. Conclusion: Results of this study suggest that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced increase in spontaneous activity and excitability of hippocampal CA1 pyramidal neurons.}, Keywords = {Epilepsy, kindling, Transcranial magnetic stimulation, Action potentials}, volume = {19}, Number = {1}, pages = {1-13}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1047-en.html}, eprint = {http://ppj.phypha.ir/article-1-1047-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {NaghaviGargari, Bahar and Behmanesh, Mehrdad and Sahraian, Mohammad Ali}, title = {Effect of Vitamin D treatment on Interleukin-2 and Interleukin-4 Genes expression in Multiple Sclerosis}, abstract ={Introduction: Multiple sclerosis is a chronic inflammatory disease of central nervous system. The etiology of MS is slightly known, but genetic and environmental factors are reported. Vitamin D regulates gene expression and affects target cell functions. The aim of this study was to investigate the expression variation of IL-2 and IL-4 genes under vitamin D supplementation in patients with multiple sclerosis. Materials and Methods: In this study, blood samples were drawn from 32 patients before and after treatment with vitamin D. Quantitative real time PCR was used to measure IL-2 and IL-4 gene expression levels. Correlation analysis between the expression levels of genes and serum vitamin D, the Expanded Disability Status Scale (EDSS) as well as other clinical features of patients with MS was performed. Results: No significant difference of IL-2 and IL-4 genes expression level was observed with vitamin D supplementation. We did not find significant correlation between IL-2 and IL-4 mRNA levels and EDSS score in multiple sclerosis patients. Conclusion: We did not find any difference between the expression of IL-2 and IL-4 genes before and after treatment with vitamin D that it may have some effects on the prevention of multiple sclerosis through other inflammatory factors and signaling pathways.}, Keywords = {Multiple sclerosis, Vitamin D, IL-2, IL-4, EDSS, qRT-PCR}, volume = {19}, Number = {1}, pages = {14-21}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1079-en.html}, eprint = {http://ppj.phypha.ir/article-1-1079-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {PirhajatiMahabadi, Vahid and movahedin, mansoureh and Mazaheri, Zohreh and Semnanian, Saeed and Mirnajafi_zadeh, Javad and Faizi, Mehr}, title = {Effects of bilateral lesion of the locus coeruleus on the sleep-wake cycle in the rat}, abstract ={Introduction: Noradrenergic cells in LC participate in the process of cortical activation and behavioral arousal. The evidence suggests that locus ceoruleus (LC) plays an important role in the sleep-wake cycle. The aim of this study was stereological estimation of cavity caused by lesion and assessment of sleep stages after bilateral lesion of the LC. Materials and Methods: Male Wistar rats weighting 250-275 gr were divided into four groups (control: n=6, sham: n=6, lesion1: n=6 and lesion2: n=6). 6 hydroxydopamine (6 OHDA) (2μg/0.5μl and 4μg/1μl) was sterotaxically injected bilaterally into LC to produced lesion. For sleep recording 3 EEG and 2 EMG electrodes were implanted respectively in the skull and dorsal neck muscle. Recordings were taken before and 7, 21 and 42 days after lesion. After 7 weeks, Rats first were anesthetized and then their brains were removed and cut in 7 μm serial sections and stained with cresyl violet. The volume of LC and the lesion induced cavity were evaluated through the stereological technique. Results: Lesion - induced cavity volume (0.5 μl) was restricted to LC, whereas Another group (1 μl), total LC and structures adjacent to the LC were also damaged. A significant decrease was seen in non-rapid eye movement (NREM) and paradoxical sleep (PS) stages and a significant increase was seen in duration of wake and paradoxical sleep without atonia (PS-A) in lesion group in comparison with control and sham groups. Conclusion: The results of this study demonstrate 2μg/0.5μl 6-OHDA is suitable dose for LC lesion and bilateral lesion of LC causing disrupt wake, NREM ,PS and also produce the PS-A.}, Keywords = {Locus Coeruleus, Bilateral Lesion Model, Sleep-Wake Cycle, 6_ hydroxydopamine.}, volume = {19}, Number = {1}, pages = {22-30}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1074-en.html}, eprint = {http://ppj.phypha.ir/article-1-1074-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ahghari, Parisa and Kadkhodaee, Mehri and Seifi, Behjat and Ranjbaran, Mina and Sedaghat, Zahra and Shams, Sedigheh}, title = {Reduction of hemorrhagic shock–induced acute kidney injury by lower limb ischemic preconditioning in rats}, abstract ={Introduction: During hemorrhagic shock (HS), the kidneys are one of the primary target organs involved. Oxidative stress is shown to be enhanced in different models of acute kidney injury (AKI). Remote ischemic preconditioning (RPC) by brief limb ischemia is considered to be a safe method to protect different organs from further damage. In this study, we investigated the effects of brief hind limb occlusion on protection against AKI and whether this protection is related to a reduction in oxidative stress. Materials and Methods: Twenty one rats were divided into three groups of seven rats. Sham-operated animals underwent surgical procedures, without hemorrhage. HS was induced by bleeding from a femoral arterial catheter to remove 44% of total blood volume. In RPC group, four cycles of lower limb ischemic preconditioning (5 min ischemia followed by 5 min reperfusion) were performed immediately before HS. Three hours later, plasma and renal tissue samples were collected for renal function monitoring and oxidative stress assessment. Results: Compared with the sham group, HS resulted in renal dysfunction, significantly increased blood urea nitrogen (BUN), plasma creatinine (Cr) and renal malondialdehyde (MDA) levels as well as decreased superoxide dismutase (SOD) activity in the kidneys (P0.05). In the RPC group, renal function was significantly improved. Plasma Cr and BUN and renal MDA levels were significantly lower in RPC group comparing to HS group (P0.05). Renal SOD activity was significantly higher in RPC group compared to HS group (P0.05). Conclusion: These results demonstrate that induction of brief periods of lower limb ischemic preconditioning improves kidney function, restores SOD activity and reduces oxidative stress injury caused by hemorrhagic shock.}, Keywords = {Remote ischemic preconditioning, Hemorrhagic shock, Kidney, Oxidative stress}, volume = {19}, Number = {1}, pages = {31-37}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1023-en.html}, eprint = {http://ppj.phypha.ir/article-1-1023-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Esmaeili-Mahani, Saeed and Satarian, Leil}, title = {Changes in regulator of G protein signaling-4 gene expression in the spinal cord of adrenalectomized rats in response to intrathecal morphine}, abstract ={Introduction: Regulators of G-protein signaling protein negatively control G protein -coupled receptor signaling duration by accelerating Gα subunit guanosine triphosphate hydrolysis. Since regulator of G-protein signaling4 has an important role in modulating morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization have not been fully clarified, the present study was designed to determine the changes in the levels of RGS4 mRNA and protein in intact and adrenalectomized (ADX) morphine-treated rats. Materials and Methods: All experiments were carried out on male Wistar rats. The tail-flick test was used to assess the nociceptive threshold and corticosterone levels were measured by radioimmunoassay. The dorsal half of the lumbar spinal cord was assayed for the expression of RGS4 using semi-quantitative RT-PCR and immunoblotting. Results: Results showed that the anti-nociceptive effect of intrathecal morphine (5 μg) was significantly increased in ADX rats. The levels of RGS4 mRNA and protein in ADX rats were similar to those in intact animals. However, morphine could elicit a significant increase in both mRNA and protein levels of RGS4 following adrenalectomy. In contrast, the pattern of RGS4 gene expression did not show significant changes in the lumbar spinal cord of intact animals after morphine injection. Conclusion: Our results demonstrate that in the absence of corticosterone, morphine increases RGS4 through promoting its gene expression.}, Keywords = {Morphine, Analgesia, RGS4, Gene expression, Corticosterone}, volume = {19}, Number = {1}, pages = {38-45}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1083-en.html}, eprint = {http://ppj.phypha.ir/article-1-1083-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Beheshti, Narjes and Ganji, Farzaneh and Sepehri, Hami}, title = {Effect of vitamin C and quercetin treatment on the liver histopathologic profile in congenital lead exposed male rat pups}, abstract ={Introduction: Lead is one of the most important environmental pollutants due to its vast use in various industries. Lead accumulation in different organs, especially the brain, liver and kidneys can cause serious health problems. Lead exposure is more dangerous during fetal period and childhood. Materials and Methods: Timed pregnant female rats divided into 6 groups. Group 1served as control group and received tap water, group 2 received 500 mg/liter lead acetate in the drinking water from 5th day of gestation up to 25th day post-partum, group 3 received the same dose of lead acetate along with daily IP injection of 40mg/kg quercetin, Group 4 received the same dose of lead acetate along with 2g/liter vitamin C, groups 5 and 6 received vitamin C and quercetin respectively like groups 2 and 3 but without lead acetate. On the 25th day postpartum, 6 male pups in each group were deeply anesthetized by chloroform livers were removed and processed for Hematoxyline- Eosin staining. The microscopic slides were photographed and liver tissue morphological characteristics were evaluated. Results: Lead exposure caused extensive histopathologic changes in liver tissue including hepatocyte degradation, cell nucleus bifurcation and inflammation around hepatic veins. Quercetin and vitamin C treatment could prevent these pathologic changes to a considerable extent. Conclusion: Vitamin C in drinking water and quercetin via IP injection could protect the liver tissue against lead hepatotoxic effects.}, Keywords = {lead exposure, liver, quercetin, vitamin C}, volume = {19}, Number = {1}, pages = {46-52}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1024-en.html}, eprint = {http://ppj.phypha.ir/article-1-1024-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ronaghi, Abdolaziz and Naderi, Nima and Motamedi, Fereshteh}, title = {Repeated administration of cannabinoid receptor agonist and antagonist impairs short and long term plasticity of rat’s dentate gyrus in vivo}, abstract ={Introduction: The effects of cannabinoids (CBs) on synaptic plasticity of hippocampal dentate gyrus neurons have been shown in numerous studies. However, the effect of repeated exposure to cannabinoids on hippocampal function is not fully understood. In this study, using field potential recording, we investigated the effect of repeated administration of the nonselective CB receptor agonist WIN55212-2, and the CB1 receptor antagonist AM251, on both short- and long-term synaptic plasticity in dentate gyrus (DG) of hippocampus. Materials and Methods: Drugs were administered three times daily for seven consecutive days into lateral ventricle of rats. Short term synaptic plasticity was assessed by measuring paired-pulse index (PPI) in DG neurons after stimulation of perforant pathway. Long-term plasticity was assessed through measurement of both population spike (PS) amplitude and field excitatory postsynaptic potential (fEPSP) slope after high frequency stimulation (HFS) of DG neurons. Results: Repeated administration of WIN55212-2 not only significantly decreased PPI in 20, 30 and 50 ms intervals but also blocked LTP. This effect was reversed by pretreatment of rats with CB1 receptor antagonist AM251. Moreover, AM251 by itself increased PPI in 10 and 20 ms interval stimulations, but had no effect on HFS-induced PS amplitude and fEPSP slope. Conclusion: These results suggest that repeated administration of cannabinoids could impair short term and long term synaptic plasticity that may be due to desensitization of cannabinoid receptors and/or changes in synaptic spine density of hippocampus which leads to alteration in short and long term memories that remains to be elucidated.}, Keywords = {Cannabinoids, short-term plasticity, long-term plasticity, hippocampus }, volume = {19}, Number = {1}, pages = {53-59}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1085-en.html}, eprint = {http://ppj.phypha.ir/article-1-1085-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Nematbakhsh, Mehdi and Azarkish, Fariba and Poorshahnazari, Ali-Asghar}, title = {Cardiovascular baroreflex sensitivity attenuates by cisplatin-induced toxicity in rats}, abstract ={Introduction: Cisplatin (CP) therapy may disturb cardiovascular system control. The objective of this study was to find baroreflex sensitivity (BRS) in CP-induced nephrotoxicity in rats. Materials and Methods: Eighteen male and female Wistar rats were randomly assigned to two groups treated with CP (2.5 mg/kg/day) and the vehicle, for five consecutive days, and then were subjected to surgical procedure to determine BRS using three different doses (0.025, 0.05 and 0.1 mg/kg) of α-adrenergic receptor agonist phenylephrine (PE). Results: Serum levels of blood urea nitrogen and creatinine, kidney weight, and kidney tissue damage score were increased in CP-treated animals. All doses of PE injection caused MAP increase and HR decrease. However, ΔMAP and ΔHR response to 0.1 mg/kg of PE were significantly lower in the CP-treated group (P<0.05). BRS also was increased in a dose-dependent manner by PE in vehicle-treated group, but this was not the case in the CP-treated animals, and significant difference in BRS was detected between the two groups (P<0.05) when 0.05 or 0.1 mg/kg of PE were infused. Conclusion: CP-induced nephrotoxicity attenuates BRS possibly due to peripheral effect on the vascular system.}, Keywords = {Cisplatin, Nephrotoxicity, Baroreflex sensitivity}, volume = {19}, Number = {1}, pages = {60-67}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1070-en.html}, eprint = {http://ppj.phypha.ir/article-1-1070-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Sepehri, Hamid and Ganji, Farzaneh and Bakhshandeh, Famemeh}, title = {Effect of short time captopril administration on spatial memory in aging rats.}, abstract ={Introduction: The brain renin-angiotensin system (RAS) has been reported having a pathological role in age-related impairment in learning and memory. Therefore, angiotensin converting enzyme inhibitors (ACEi) are expected to have positive effects on memory. Longtime treatment with captopril (an angiotensin converting enzyme inhibitor) significantly attenuates the age-related impairment in learning and memory. Methods: In the present study, 24 month old male Wistar rats were divided into four experimental groups (n=8). Captopril treated groups received daily ip injections of captopril at doses of 5, 10, 15 mg/kg/day for one week, the forth group served as control and remained untreated. Learning process was assessed by the reference memory task in the Morris water maze. All rats received water maze training (4 trials/day for 5 days) to assess hippocampal dependent spatial learning and then received a 60-s probe test of spatial memory retention 24 h after the 20th trial. Results: Over 5 days of training, captopril 5, 10, 15 mg/kg/day treatment significantly reduced the latency and path length to finding the escape platform. In probe trails (without platform), on the last day of training, the captopril -treated group spent significantly longer time in the platform quadrant than control animals. Among treated group, 10 /mg/Kg dosage of captopril induced the best rehearsals memory. Conclusion: These results confirm the previous studies that ACEi have a positive influence on memory and it was noticeable that even short time treatment by captopril can improve spatial memory in the aged rats.}, Keywords = {Angiotensin converting enzyme, memory, captopril, Morris water maze, aging}, volume = {19}, Number = {1}, pages = {68-75}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1062-en.html}, eprint = {http://ppj.phypha.ir/article-1-1062-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Mohammadi, Ekram and Bigdeli, Mohammad Rez}, title = {Time course of normobaric hyperoxia preconditioning on NCX2, 3 expression}, abstract ={Introduction: The purpose of this study was to determine Na-Ca exchanger 2, 3 (NCX2, 3) protein level changes during 2, 5, 10, 15 days after induction of normobaric hyperoxia (HO) preconditioning. Materials and Methods: Rats were divided in two experimental groups. The first group was exposed to 95% inspired HO for 4 h/day for 6 consecutive days (HO). The second group acted as control, and was exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) subgroups. After 2, 5, 10 and 15 days from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 hours reperfusion, neurologic deficit score (NDS) and infarct volume (IV) were measured in MCAO-operated subgroups. The NCX 2, 3 expression levels of core, penumbra and subcortex regions were assessed in sham-operated and intact subgroups. Results: Expression of NCX 2, 3 proteins were increased in penumbra (P=0.000, P=0.002), core (P=0.001, P=0.033) and just NCX3 was increased in subcortex (P=0.033) during preconditioning with HO. Neurologic deficit score and infarct volume were decreased with HO preconditioning. These effects of hyperoxia disappeared gradually during 15 days after pretreatment. Conclusion: Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO durable effects on NCX2, 3 expression, IV and NDS are consistent with an active role in the genesis of ischemic neuroprotection.}, Keywords = {hyperoxia, brain ischemia tolerance, neuroprotection, NCX2, NCX3}, volume = {19}, Number = {2}, pages = {76-89}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1093-en.html}, eprint = {http://ppj.phypha.ir/article-1-1093-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Malakoutikhah, Mahboobeh and Satarian, Leila and Kiani, Sahar and Javan, Mohamm}, title = {Alpha-Tocopherol increases the proliferation of induced pluripotent stem cell derived neural progenitor cells}, abstract ={In addition to its antioxidant effect, Vitamin E or α–tocopherol is suggested to enhance remyelination in the animal model of non-inflammatory demyelination. In this study, the possible proliferative effect of vitamin E on human- induced pluripotent stem cell-derived neural progenitors (hiPS-NPs) and the underlying mechanisms were investigated in vitro. NPs were induced from iPS cells via 3 steps within 18 days and then characterized for NPs markers NESTIN, SOX1 and OTX2. MTT assay was used to compare cell populations. LY294002, U0126 and PP2 were used for selective inhibition of enzymes PI3K, MEK and Src-kinase, respectively. Vitamin E increased hiPS-NPs proliferation after 24 and 48 h exposure. The inhibition of both PI3K/Akt and Src-kinase signaling pathways counteracted the effect of vitamin E of NPs. Our data suggest that vitamin E may enhance NPs proliferation via activating PI3K and Src-kinase and may enhance myelin repair following demyelinating Injuries.}, Keywords = {Neural progenitor cells, Cell proliferation, Vitamin E, α –tocopherol, PI3-kinase, Src-kinase}, volume = {19}, Number = {2}, pages = {90-98}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1100-en.html}, eprint = {http://ppj.phypha.ir/article-1-1100-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Khakpay, Roghaieh and Azaddar, Maryam and Khakpai, Fatemeh and HatamiNemati, Homeir}, title = {The role of GABAA receptors in the analgesic effect of intra-paragigantocellularis lateralis injection of 17β-estradiol in male rat}, abstract ={Introduction: 17;beta-Estradiol modulates nociception by binding to the estrogenic receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABAA receptors. In addition to its autonomic functions, paragigantocellularis lateralis (LPGi) is involved in the pain modulation, too. The aim of the current study was to investigate the involvement of the membrane-bound GABAA receptors in the pain modulatory effect of intra- LPGi injection of 17;beta-estradiol of male rats. Materials and Methods: This study was performed using male Wistar rats in the range of 200-270 g. In order to investigate the antinociceptive effect of intra-LPGi microinjection of 17;beta-estradiol, cannulation into the LPGi nucleus was performed. 500 nl of drugs were administered 15 minutes prior to formalin injection (50 ;mul of 4%). Then, formalin-induced paw jerking behaviour was recorded for 60 min. For assessing the role of the GABAA receptors in the estradiol induced pain modulation, 17;beta-estradiol was administered into the LPGi nucleus 15 min after the injection of 25 ng/;mul bicuculline and paw jerking frequency was recorded for 1 h. Results: The results of the current study showed that intra-LPGi injection of 0.8 ;mumol of 17;beta-estradiol attenuated the chronic phase (P<0.001) of paw jerking behaviour. Bicuculine -the GABAA receptor antagonist- significantly reduced the antinociceptive effect of intra-LPGi 17;beta-estradiol in the chronic phase (P<0.001). Conclusion: It may be concluded that the analgesic effect of intra-LPGi injection of 17;beta-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.}, Keywords = {17β-Estradiol, Paragigantocellularis lateralis nucleus, GABAA receptor, Pain}, volume = {19}, Number = {2}, pages = {99-106}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1101-en.html}, eprint = {http://ppj.phypha.ir/article-1-1101-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Plotnikov, Evgenii and Korotkova, Elena and Voronova, Olesya and Dorozhko, Elena and Bohan, Nikolay and Plotnikov, Sergey}, title = {Lithium-based antioxidants: electrochemical properties and influence on immune cells}, abstract ={Introduction: Lithium salts are known as effective psychotropic medicine for treatment bipolar disorder and may be used to treat alcoholism, schizoaffective disorders, and cluster headaches. The antioxidant activity and immunomodulatory effects of prospective lithium compounds have been investigated in this work. Materials and Methods: The antioxidant properties were studied by the voltammetry method. Influence of the lithium compounds on the immune cells of human blood were determined by measuring phagocytic activity of leucocytes and by the rate of blastic transformation of lymphocytes. Results: Relatively better antioxidant and immunotropic properties have been revealed for lithium ascorbate, compare to widely used drug-lithium carbonate. Lithium aspartate revealed antioxidant activity, as well. Conclusion: Studied lithium salts can be considered as prospective psychotropic antioxidant with immunomodulatory effects. The combination of these properties significantly extends the potential medical applications of lithium salts.}, Keywords = {antioxidant activity, immunomodulatory effects, voltammetry, lithium ascorbate, lithium aspartate }, volume = {19}, Number = {2}, pages = {107-113}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1098-en.html}, eprint = {http://ppj.phypha.ir/article-1-1098-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Almasi, Shohreh and Shahsavandi, Behnaz and Aliparasty, Mohammad Reza and Alipour, Mohammad Reza and Rahnama, Badrossadat and Feizi, Hadi}, title = {The anti-apoptotic effect of ghrelin in the renal tissue of chronic hypoxic rats}, abstract ={Introduction: Ghrelin is an endogenous peptide that has diverse functions in the body. One of the newly recognized roles of this peptide is its antiapoptotic effect. However, this function has not been investigated in normobaric hypoxia- induced apoptosis in body organs. This study will examine the effect of ghrelin treatment on Bax-Bcl-2 gene expression in the kidney of chronic hypoxic rats. Materials and Methods: Male Wistar rats in three experimental groups normal, hypoxic+saline and hypoxic+ghrelin were used in this study. The expression level of Bax and Bcl-2 genes were measured by Real-Time PCR. The Bax/Bcl-2 ratio was also compared in three groups statistically. Results: Chronic hypoxia decreased the Bcl-2 gene expression (p<0.01), and increased the Bax/Bcl-2 ratio (p<0.05). Ghrelin treatment decreased the Bax/Bcl-2 ratio through upregulation of Bcl-2 gene (p<0.05). Conclusion: It seems that ghrelin has an antiapoptotic effect on the kidney of animals that live in a chronic hypoxic state. Which could potentially introduce a therapeutic role for this peptide.}, Keywords = {Ghrelin, Chronic Hypoxia, Apoptosis, Kidney, Rat}, volume = {19}, Number = {2}, pages = {114-120}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1092-en.html}, eprint = {http://ppj.phypha.ir/article-1-1092-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Esmaeilpour, Khadijeh and Sheibani, Vahid and Saadati, Hakimeh}, title = {Caffeine improved spatial learning and memory deficit in sleep deprived female rat}, abstract ={Previous studies have shown that caffeine has beneficial effects on cognitive impairment in sleep deprived male rats. Therefore in the present study, we examined the effects of chronic caffeine administration on learning and memory impairments induced by sleep deprivation (SD) in the intact and ovarectomized (OVX) female rats. Two sets of animals including intact and OVX were randomly recruited into the following subgroups: control, SD, wide platform (Sham platform), caffeine, and caffeine plus SD. Multiple platform method was used for SD induction. Spatial learning and memory were determined using Morris water maze (MWM) task. Throughout behavioral investigation, significant learning impairment was observed in sleep-deprived OVX rats compared to the intact and the other OVX groups (P<0.05). Short term memory impairment was observed in both sleep-deprived OVX and intact groups (P<0.05). 4weeks caffeine administration improved these impairments. Based on these findings we propose that sleep deprivation impaired cognitive function whereas caffeine treatment reversed these impairments.}, Keywords = {Sleep deprivation, caffeine ,Morris water maze, Female rats}, volume = {19}, Number = {2}, pages = {121-129}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1097-en.html}, eprint = {http://ppj.phypha.ir/article-1-1097-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Esmaeili, Mohammad Hossein and Dargahi, Tahereh and Haghdoost-Yazdi, Hashem}, title = {Normobaric hyperoxia preconditioning attenuates streptozotocin - induced impairments in spatial learning}, abstract ={Introduction: A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer;#39s disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)- induced memory impairment in rats. Materials and Methods: Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. Results: STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Conclusion: Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits.}, Keywords = {Alzheimer\'s Disease, Streptozotocin, Hyperoxia Preconditioning, Morris Water Maze, Probe test}, volume = {19}, Number = {2}, pages = {130-138}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1087-en.html}, eprint = {http://ppj.phypha.ir/article-1-1087-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Jelodar, Gholamali and Rafiee, Bahare and Moosavi, Seyed Hami}, title = {Silymarine extract improved plasma homocysteine, lipids and liver enzymes in hyperhomocysteinemic Non-alcoholic Steatohepatitis}, abstract ={Introduction: Silymarine extract is currently prescribed by some physicians for treatment of fatty liver disease. In the present study, the effect of administration of tablet containing silymarine extract on plasma homocysteine (Hcy), folate, vitamin B12 and liver enzymes activity in non-alcoholic steatohepatitis (NASH) was investigated. Materials and Methods: Seventy-four patients (40 female and 34 male aged 32-44 years) who were diagnosed with NASH and hyperhomocysteinemic by liver biopsy, measurement of liver enzymes activity and plasma Hcy were recruited for this study. The patients were not consuming alcohol or taking any other medications/medicines. Plasma Hcy, folate, B12, cholesterol, triglyceride, fasting glucose, aspartate aminotransferase (AST) and alaninaminotransferase (ALT) activity of all patients were measured before and after treatment. Tablet containing silymarine extract (140mg∕kg) was administrated thrice /three times a day for 2 months. Results: The results showed a significant reduction in the level of plasma Hcy, cholesterol, triglyceride, fasting glucose (P <0.05) following the administration of tablet containing silymarine extract, however, the increase in plasma folate and B12 levels was not significant. The results did not demonstrate any significant negative correlations between Hcy and B12, and also between Hcy and folate. Conclusion: It can be concluded that consumption of tablet containing silymarine extract in NASH patients significantly reduces level of plasma Hcy, cholesterol, triglyceride, fasting glucose and AST and ALT activity, while level of plasma folate and B12 remained unchanged.}, Keywords = {Silymarine, homocysteine, non-alcoholic steatohepatitis, liver enzyme}, volume = {19}, Number = {2}, pages = {139-145}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1086-en.html}, eprint = {http://ppj.phypha.ir/article-1-1086-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ashabi, Ghorbangol and Khodagholi, Fariba and Zare-shahamati, Shima and Ghadernezhad, Negar and Maleki, Mona and Khalaj, Leil}, title = {A comprehensive approach to investigate the contradictory effects of metformin therapy in cerebral ischemic injury}, abstract ={Ischemic brain injury involves a complex sequence of excitetoxic and oxidative events. Metformin is proposed as one of the potential candidates for returning the body to its basic homeostasis in ischemic situations. Metformin can either protect or damage cells by activating AMP-activated protein kinase (AMPK) and its downstream factors so, it has a dual role in the cerebral ischemia context, but more investigations are needed to define its exact underlying mechanism. Herein, we classify the controversial results of metformin therapy in the experimental models of brain ischemia central and peripheral injection of metformin, chronic and acute treatment, pre- and post-treatment with metformin, tissue-specific role of metformin, dose-specific effect of metformin, age-dependent aspects of metformin therapy. Categorizing different types of cerebral ischemia is important in investigating the dual role of metformin. Due to the variations in metformin therapy, it can be used for chronic treatment, but the patients must be informed about its harmful effects. Although the mechanisms in which AMPK protects/degenerates neurons against ischemic stress situation are still unknown.}, Keywords = {Metformin, AMPK, Glucose, Brain, Ischemia}, volume = {19}, Number = {3}, pages = {146-157}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1124-en.html}, eprint = {http://ppj.phypha.ir/article-1-1124-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ashoori, Mohammad Reza and Bathaie, S. Zahra and Heidarzadeh, Hami}, title = {Long-term, high-dose aspirin therapy increases the specific activity of complex III of mitochondrial respiratory chain in the kidney of diabetic rats}, abstract ={Introduction: One of the main mechanisms by which diabetic complications occur is an alteration of the structure and function of proteins due to hyperglycemia. Aspirin (ASA) affects cellular pathways through different mechanisms, including glycation inhibition and antioxidant activity. The aim of the present study, as a follow up to our previous one, is to investigate the effect of long-term, high-dose ASA therapy on mitochondrial respiratory chain complexes in the kidneys and brain of streptozotocin-induced diabetic rats. Its effect on liver toxicity of the rats was also investigated. Materials and Methods: High dose of ASA (100 mg/kg in drinking water) was administered to streptozotocin-induced diabetic rats during the twelve-week study period. After that, the rats were sacrificed under anesthesia and the tissues were retained -80 °C. Then the activity of respiratory chain complexes and the mentioned enzyme were measured in the brain, kidney, liver and serum of rats. Results: Treatment of diabetic rats with ASA could significantly compensate for the decreased activity of complex III respiratory chain in the kidneys. In addition, the activity of the liver enzymes (ALT, AST, ALP and LDH) in the serum of diabetic rats was significantly reduced by administration of ASA. However, there were no other significant functional changes observed in the kidney and brain respiratory chains complexes and the mentioned enzymes in liver. Conclusion: In conclusion, ASA therapy has a beneficial effect on the mitochondrial complexes and some serum enzymes in diabetic rats.}, Keywords = {Aspirin, Streptozotocin, Respiratory Chain Complex, Brain, Kidney, Liver Enzymes}, volume = {19}, Number = {3}, pages = {158-166}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1099-en.html}, eprint = {http://ppj.phypha.ir/article-1-1099-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Hassanzadeh, Parichehr and Arbabi, Elham and Rostami, Fatemeh and Atyabi, Fatemeh and Dinarvand, Rassoul}, title = {Carbon nanotubes prolong the regulatory action of nerve growth factor on the endocannabinoid signaling}, abstract ={Introduction: Carbon nanotubes (CNTs) have shown enormous potential in neuroscience. Nerve growth factor (NGF)-CNTs complex promotes the neuronal growth, however, the underlying mechanism(s) have remained elusive. Based on the interplay between NGF and the endocannabinoid system, involvement of the neuroprotective endocannabinoid, 2-arachidonoyl glycerol (2-AG), was investigated in the mechanism of action of NGF. Materials and Methods: Multi-walled CNTs (MWCNTs)-NGF complex was prepared using amino-functionalized COOH-MWCNTs. MWCNTs were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). In vitro cytotoxicity was evaluated by MTT assay. Following three times daily intracerebroventricular injections of NGF solution (2, 5, and 10 &mug), and 5, 10, and 20 &mug of acid- or amine-modified MWCNTs, or MWCNTs-NGF complex for either one or 7 days, 2-AG contents were quantified in the frontal cortex and hippocampus of rats by isotope-dilution liquid chromatography/mass spectrometry. Results: FTIR confirmed the amino-functionalization of COOH-MWCNTs and NGF immobilization on the aminated MWCNTs. Aminated MWCNTs and MWCNTs-NGF complex showed less cytotoxicity than COOH-MWCNTs (P<0.05, P<0.01, and P<0.01). Chronic, but not acute, administration of MWCNTs-NGF complex and NGF solution at the highest dose tested led to the elevation of 2-AG at 1 h from the last injection (P<0.01 and P<0.001). 2-AG enhancement induced by MWCNTs-NGF complex lasted for up to 5 and 12 h post-injection (P<0.01 and P<0.001). 2-AG contents remained at the baseline level in the sham and groups receiving vehicle, acid- or amine-modified MWCNTs (P>0.05). Conclusion: Functionalized MWCNTs-NGF complex induces a long-lasting increase of brain 2-AG content indicating the efficiency of this nanostructure to provide a sustained concentration of NGF. Implication of 2-AG in the mechanism of action of NGF might be of great therapeutic significance in the neurological disorders.}, Keywords = {Carbon nanotubes, Nerve growth factor, Endocannabinoid signaling}, volume = {19}, Number = {3}, pages = {167-176}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1112-en.html}, eprint = {http://ppj.phypha.ir/article-1-1112-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Beheshti, Siamak and Eivani, Mehdi and Moshtaghian, Jamal}, title = {Gap junctions of the hippocampal CA1 area are crucial for memory consolidation}, abstract ={Introduction: Gap junctions are specialized cell–cell contacts between eukaryotic cells through which they communicate. This type of communication has the potential to modulate memory process. We evaluated the effects of the gating of the hippocampal CA1 area gap junction channels on memory consolidation, using passive avoidance task. Materials and Methods: 72 adult male Wistar rats were distributed into 9 groups of 8 each. Two guiding cannulas were bilaterally implanted in the hippocampal CA1 area of all rats. One week after surgery, the animals received an electrical shock with the intensity and duration of 0.3 mA and 1s, respectively. Immediately after training 25, 75 or 150 nM doses of carbenoxolone, a non-selective blocker of gap junction channels or 50, 150 and 1500 nM doses of trimethylamine, an opener of gap junction channels were injected. Another group received 50 nM trimethylamine and 10 min later 75 nM carbenoxolone, immediately post-training. 24 hours later, memory retrieval was assessed. Results: Post-training injection of carbenoxolone significantly and dose- dependently decreased step-through latency, whereas post-training injection of trimethylamine showed a tendency toward increasing step-through latency. Post-training injection of trimethylamine (50 nM) increased step-through latency, significantly compared with post-training injection of carbenoxolone (75 nM and 150 nM). Post-training injection of trimethylamine (50 nM) before carbenoxolone (75 nM) reversed the effects of carbenoxolone on inhibition of memory consolidation. Conclusion: These data suggest that the intercellular coupling via gap junction channels in the hippocampal CA1 cells is crucial for memory consolidation in the passive avoidance task.}, Keywords = {Gap junction, Memory, Hippocampal CA1 area, Passive avoidance task}, volume = {19}, Number = {3}, pages = {177-184}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1122-en.html}, eprint = {http://ppj.phypha.ir/article-1-1122-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Eidelkhani, Nastaran and Radahmadi, Maryam and Rafiee, Laleh and Gharzi, Mahsa and Alaei, Hojjatallah and Reisi, Parham}, title = {Effects of doxepin on spatial memory, TNF-α and Bcl-2 family genes expression in rat hippocampus}, abstract ={Introduction: Although the initial hypothesis for the action of doxepin was based on the inhibition of the reuptake of neurotransmitters, it has been suggested that it may also involve other mechanisms. Therefore, this study aims to investigate the effect of doxepin on spatial memory, tumor necrosis factor alpha (TNF-;alpha) level, expression of pro-apoptotic (Bad and Bax) and anti-apoptotic (Bcl-2) genes in the rat hippocampus. Materials and Methods: Male rats were divided randomly into three groups the control, the doxepin 1 and 5 mg/kg, respectively). Rats received i.p injection of doxepin for 21 days. Spatial memory was evaluated by Morris water maze test. Then the hippocampi were dissected for measurement of the expression of Bcl2, Bad and Bax genes and the TNF-;alpha level. Results: Our results showed no significant effects of doxepin on spatial memory. Doxepin significantly decreased expression of Bad gene, but had no significant/considerable effects on Bcl2 and Bax gene expression. Also, the ratio of TNF-;alpha to total protein (%) did not show significant differences in the rat hippocampus. Conclusion: These results did not show any significant impact of doxepin on the factors affecting the neuronal functions in intact animals. However, Since a significant reduction in the hippocampal Bad mRNA levels was observed It is our assumption that doxepin has neuroprotective effects.}, Keywords = {Doxepin, Memory, Hippocampus, Bcl-2 family, TNF-α.}, volume = {19}, Number = {3}, pages = {185-192}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1130-en.html}, eprint = {http://ppj.phypha.ir/article-1-1130-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Lashkarizadeh, Mohammad Reza and Garshasbi, Mohammad and Dabiri, Shahriar and Lashkarizadeh, Mahdieh and Shabani, Mohamm}, title = {Evaluation of wound healing and post-operative intra-abdominal adhesions in opium addicted rats}, abstract ={Introduction: Opium addiction can change immune response to Types of stress such as injury or trauma due to alterations in the in secretion status of cytokines in the body. In this study, effects of opium addiction on wound healing and post-operative adhesion bands were assessed after laparotomy. Materials and Methods: Male rats (n=20) were randomly divided into opium addicted (documented with Naloxone test) and control group. Three weeks after surgery, site of abdominal incision was excised elliptically and sent for wound healing grading assessment by pathologist and an intra-abdominal adhesion band assessment was done. The concentrations of three cytokines (TNF , IFN and IL10) were also measured before, immediately after surgery and 24 hour after surgery. Results: Post-operative intra-abdominal adhesion was decreased in opium addicted group in comparison to control group (p value = 0.014). No statistically significant difference was found in the wound healing phase in two groups (P value = 0.057). Our findings showed that serum level of TNF , IFN and IL10 in two groups measured in all phases of examination (before surgery, within 30-60 min after surgery and 24h after surgery), were not statistically different/significant (p>0.05). Conclusion: Since opium addiction can decrease post-operative intra-abdominal adhesions in rats, they may be susceptible to increased inflammation and these effects may be due to decreased post-operative pain.}, Keywords = { Opium Addiction, Laparotomy, Wound healing, Adhesion, Rats}, volume = {19}, Number = {3}, pages = {193-199}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1127-en.html}, eprint = {http://ppj.phypha.ir/article-1-1127-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Babaei, Parvin and PourrahimGhouroghchi, Ameneh and Damirchi, Arsalan and SoltaniTehrani, Bahram}, title = {The interactive effect of aerobic-resistance training and estrogen therapy on metabolic syndrome indices and omentin-1}, abstract ={Introduction: Obesity and visceral fat accumulation after menopause are associated with insulin resistance and cardiovascular diseases. We investigated the interactive effect of aerobic-resistance training and estrogen replacement therapy on visceral fat, omentin-1 and HOMA-IR in ovariectomized rats. Materials and Methods: Fifty female Wistar rats were ovariectomized (OVX) and divided into 5 groups (n=10 rats per group): Ovx+sedentary (Sedentary), aerobic-resistance training (Ovx+Exe), aerobic-resistance training+estrogen replacement therapy (Ovx+Exe+Est), estrogen replacement therapy (Ovx+Est) and sesame oil (Ovx+Oil). The exercise consisted of 8-week aerobic-resistance training (20 m/min, 3 days/week, 60 min/day, 10% slope, Load 3% body weight).17b-estradiol valerate (30 ;mug/kg bw in 0.2 ml sesame oil) were injected subcutaneously, three days a week during 8 weeks and the Ovx+Est+Est received both exercise protocol and estradiol as previous groups. Obtained data were analyzed by ANOVA and post hoc Tukey test. Results: Omentin-1showed significant increase in Ovx+Exe compared to Ovx+Exe+Est and Ovx+Est (P<0.05). HOMA-IR and visceral fat was decreased in Ovx+Exe, Ovx+Exe+Est compared to Sedentary (P<0.05). Conclusion: Eight-week aerobic-resistance training, 17-b estradiol replacement and co-treatment of exercise+estrogen successfully decreased visceral fat and insulin resistance probably via elevation in omentin-1 in ovaryectomized rats. Regarding the risk of hormone replacement therapy this study suggests that 2- month aerobic-resistance training is more effective in treating metabolic syndrome, rather than estrogen replacement therapy.}, Keywords = {Combined Exercise, Hormone Therapy, HOMA-IR, Omentin-1, Visceral Adipose}, volume = {19}, Number = {3}, pages = {200-207}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1120-en.html}, eprint = {http://ppj.phypha.ir/article-1-1120-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Nasimi, Parva and Tabandeh, Mohammad Reza and Vahdati, Akbar and Khatamsaz, Saee}, title = {Busulfan induces oxidative stress- and Bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice}, abstract ={Introduction: Busulfan as a chemotherapeutic agent causes testicular germinal epithelium depletion and cytotoxicity in germ cells. The aim of this study was to assess antioxidant status, reactive oxygen species (ROS) generation and apoptosis-related genetic markers of adult male mouse sperm following busulfan treatment. Materials and Methods: Forty adult NMRI mice (30 ± 5 g) were divided into two groups. Control and busulfan treated group were administered with 100 &muL dimethyl sulfoxide and 3.2 mg/kg/day busulfan for 4 days, respectively. The superoxide dismutase and glutathione peroxidase assays were used for analyzing antioxidant status. Then, the levels of Bcl-2 family gene expression, lipid peroxidation and cytotoxicity were evaluated by Real-Time PCR, thiobarbituric and lactate dehydrogenase assays, respectively. Results: The results showed significant decrease on antioxidant status, increase on lipid peroxidation and lactate dehydrogenase in epididymal sperm and testis of busulfan treated mice in comparison with control (P< 0.05). Real Time PCR demonstrated significantly increased-Bax gene expression and decreased-Bcl-2 gene expression in epididymal sperm of treated group (P< 0.05). Conclusion: The high levels of lipid peroxidation and lactate dehydrogenase revealed increased-ROS and severe cytotoxicity in epididymal sperm and testis tissue following busulfan treatment at clinical dose. The oxidative stress and increased-ROS may induce Bcl-2 family gene expression-related apoptosis following busulfan therapy in normal cells.}, Keywords = {Apoptosis, Bcl-2 family genes, Busulfan, Epididymal sperm, Oxidative stress.}, volume = {19}, Number = {3}, pages = {208-215}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1123-en.html}, eprint = {http://ppj.phypha.ir/article-1-1123-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ivanova, Svetlana A and Fedorenko, Olga Yu and Freidin, Maxim B and Alifirova, Valentina M and Zhukova, Natalia G and Zhukova, Irina A and AlHadithy, Asmar FY and Brouwers, Jacobus RBJ and Bokhan, Nikolay A and Wilffert, Bob and Loonen, Anton JM}, title = {Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia}, abstract ={Introduction: Long-term levodopa treatment of Parkinson’s disease (PD) is frequently complicated by spontaneously occurring involuntary muscle movements called dyskinesia. The exact pathological mechanism of this complication has not yet been elucidated. We have previously demonstrated that in PD patients the vulnerability to develop peripheral but not orofacial dyskinesia is associated with the presence of two variants of the GRIN2A gene. Moreover, we have shown that in tardive dyskinesia (TD) orofacial dyskinesia is associated with other polymorphisms as compared with peripheral dyskinesia. In the present study we investigate whether the peripheral versus orofacial nature of levodopa-induced dyskinesia (LID) in PD can be explained by considering polymorphisms for dopaminergic and serotonergic receptors. Materials and Methods: 101 Russian patients with PD (38M/63F) were examined. Genotyping was carried out on 19 SNPs for 3 neurotransmitter genes: 10 SNPs for DRD3 gene (rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771), 1 SNP for DRD4 gene (rs3758653), and 8 SNPs for HTR2C gene (rs6318, rs5946189, rs569959, rs17326429, rs4911871, rs3813929, rs1801412, rs12858300). Results: Genotyping patients with PD and LID revealed that only rs3773678 (DRD3, dominant, p = 0.042) was associated with orofacial dyskinesia. Conclusion: The findings of the current study are not related to LID in PD itself, but to other forms of orofacial dyskinesia in this patient group.}, Keywords = {Levodopa-induced dyskinesia, Parkinson’s disease, Dopaminergic receptors, Serotonergic receptors, Genetic variants}, volume = {19}, Number = {4}, pages = {216-221}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1139-en.html}, eprint = {http://ppj.phypha.ir/article-1-1139-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Champaneri, Viral I and Kathrotia, Rajesh}, title = {A study of variation in cardiocirculatory parameters with different body positions during isometric exercise in young adult males.}, abstract ={Introduction: To study the effects of exercise, how important it is to choose a posture? We aimed to characterize the possible impact of different body positions on cardiovascular parameters during and after sustained isometric handgrip (IHG) exercise. Materials and Methods: Cross sectional study was carried out in 33 young adult males (mean age: 19.21±1.083 years). We recorded Blood Pressure (BP), Heart Rate (HR) and SpO2 at rest, 1st minute of exercise, at 3rd minute of exercise or prior to failure and at 2 minutes after IHG exercise at 30% of Maximum voluntary contraction (MVC) in sitting, supine and standing positions. Mean arterial pressure (MAP), Pulse pressure (PP) and Rate pressure product (RPP) were calculated from BP and HR data. Results: SBP, DBP, MAP, HR and RPP increased significantly during 1st and 3rd min of exercise and returned to resting level at 2 min after exercise in all three postures. During resting period and at 2 min after IHG exercise SBP and PP were significantly higher in supine compared with sitting and standing position, while DBP, HR and RPP were significantly increased in standing position. DBP, PP, MAP and HR changed significantly in supine, sitting and standing posture with time of exercise (two-way repeated measure ANOVA). Conclusion: IHG exercise leads to an across the board increase of all the cardiovascular parameters. The effect of posture was more pronounced at rest and during initial duration of exercise. Thus, posture may be a factor to consider in testing initial response during IHG exercise, but not for studying effects of prolonged duration of exercise.}, Keywords = {Isometric handgrip exercise, Body positions, Blood pressure, Heart rate, Rate pressure product}, volume = {19}, Number = {4}, pages = {222-231}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1136-en.html}, eprint = {http://ppj.phypha.ir/article-1-1136-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Adikwu, Elias and Braimbaifa, Nelson and Obianime, Atuboyedia Wolfe}, title = {Melatonin and Alpha Lipoic Acid: Possible Mitigants for Lopinavir/Ritonavir- Induced Renal Toxicity in Male Albino Rats}, abstract ={Introduction: This study evaluated the effects of pretreatments with melatonin (MT), and Alpha Lipoic acid (ALA) on lopinavir/ritonavir (LPV/r) -induced serum levels of creatinine (Cr), urea (U), uric acid (Ua) and kidney levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in male albino rats. Effects of treatments with MT and ALA were also evaluated on baseline levels of the above parameters. Materials and Methods: Adult male albino rats orally received MT (10mg/kg), ALA (10mg/kg) and LPV/r (22.9/5.71, 45.6/11.4 and 91.4/22.9mg/kg) for 60 days. At the end of drug treatment animals were sacrificed, serum was extracted and evaluated for Cr, U, and Ua. Kidney was harvested and evaluated for MDA, SOD, CAT and GSH. Results: Treatment with MT and ALA significantly (p<0.05) decreased baseline serum levels of Cr, U, Ua and kidney MDA level while kidney levels of SOD, CAT and GSH were decreased when compared to the control. On the contrary, treatment with LPV/r significantly (p<0.05) and dose -dependently increased serum Cr, U, Ua levels and kidney MDA level while kidney levels of SOD, CAT and GSH were decreased when compared to the control. But pretreatments with MT and ALA mitigated LPV/r induced changes in all evaluated parameters. Pronounced mitigation was observed with pretreatment using a combination of MT and ALA. Conclusion: Observations in this study may be due to the oxidant effect of LPV/r and the antioxidant effects of MT and ALA. This study, therefore recommends MT and ALA as treatment or prevention for LPV/r induced renal toxicity.}, Keywords = {Kidney, Toxicity, Lopinavir/Ritonavir, Melatonin, Alpha Lipoic Acid, Rats}, volume = {19}, Number = {4}, pages = {232-240}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1133-en.html}, eprint = {http://ppj.phypha.ir/article-1-1133-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Dehghani, Farzane and Reisi, Parham}, title = {Acute application of cholecystokinin and its effect on long-term potentiation induction at CA1 area of hippocampal formation in rat}, abstract ={Introduction: It has been demonstrated that cholecystokinin sulfated octapeptide (CCK-8s) can affect synaptic transmission in the hippocampus. Because one of the major experimental models to understand the events happening in synaptic plasticity is To Study the long-term potentiation (LTP), we decided to investigate the effect of concomitant administration of CCK-8s and tetanic stimulation of Schaffer collateral path-CA1 synapses on LTP induction and maintenance. Materials and Methods: Experimental groups were control, CCK-5min and CCK-30min. CCK-8s was injected 5 or 30 min (1.6 μg/kg; i.p.) prior to induction of LTP. The stimulating and the recording electrodes were placed in the Schaffer collateral pathway and hippocampal CA1, respectively. LTP was induced by 100 Hz tetanization and field excitatory postsynaptic potentials (fEPSP) slope, area and amplitude were measured and compared during 30 minutes Interval before, and 90 minutes Interval after LTP induction in each group. Results: The results showed that maintenance of the induced LTP was significantly improved in the CCK-30min group comparing to the control group. This improvement was particularly visible in the fEPSP slope (p<0.001) and the fEPSP area (p<0.001). Seventy minutes after the LTP induction, fEPSP was similar in both the CCK-5min and the CCK-30min groups and there was Also a significant difference between the treated groups comparing to the control group (p<0.05). Conclusion: These results indicated that LTP induction and maintenance is carried out effectively, at higher levels of CCK in the brain. The data suggest that CCK-8s has pronounced effects on synaptic plasticity in the hippocampus and the consequent cognitive functions.}, Keywords = {Cholecystokinin sulfated octapeptide, CA1, Hippocampus, LTP.}, volume = {19}, Number = {4}, pages = {241-246}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1132-en.html}, eprint = {http://ppj.phypha.ir/article-1-1132-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Plotnikov, Evgenii and Pehenko, Vladimir and Plotnikov, Vladimir}, title = {Antibacterial and Immunomodulatory Effects of Hexamethylenetetramine (Methenamine) Silver Nitrate}, abstract ={Introduction: Currently, developing new antibacterial drugs as alternative antibiotics is a very active area of research, due to widspreading widespread prevalence of resistant strains of microorganisms. This work intends to investigate of antibacterial properties and influence on immune blood cells of the silver-based compound hexamethylenetetramine (methenamine) silver nitrate with general formula [Ag(CH2)6 N4]NO3. Materials and Methods: The antibacterial effect of the silver complex was investigated by agar diffusion and serial dilution methods. Silver complex have been investigated for its impact on the phagocytic activity of neutrophils and on immune cells during the reaction of blast transformation of lymphocytes (RBTL). Results: Studies have shown that hexamethylenetetramine silver nitrate possesses both bactericidal and bacteriostatic dose-dependent effect on tested bacterial strains, including Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Streptococcus pneumoniae. Escherichia coli were shown to be the most susceptible bacteria. Cytotoxic effect of silver salt on lymphocytes was detected in high dosage in RBTL. No significant immunosuppressive impact on neutrophils phagocytic activity of tested complex was shown. Conclusion: Agents of nosocomial infections were highly susceptible to the drug. Complex has proved to be promising as a prospective antibacterial drug with wide range of activity.}, Keywords = {Silver-based complex, Methenamine, Antibacterial drug, Nosocomial infections, Staphylococcus, Streptococcus, Silver hexamethylenetetramine, Phagocytosis, Lymphocytes blast transformation}, volume = {19}, Number = {4}, pages = {247-252}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1135-en.html}, eprint = {http://ppj.phypha.ir/article-1-1135-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Ashabi, Ghorbangol and Khalaj, Leil}, title = {Gemfibrozil protect PC12 cells through modulation of Estradiol receptors against oxidative stress}, abstract ={Introduction: Neurodegenerative diseases are progressive disorders that could impair neuronal functions and structures. Oxidative stress and mitochondrial dysfunction are involved in the etiology of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and etc. Gemfibrozil is used as a therapeutic drug for hyperlipidemia. It has been shown that gemfibrozil is neuroprotective via modulation of mitochondrial biogenesis pathway under oxidative stress condition and in a sex-dependent manner. Materials and Methods: In this study, neuronal-like PC12 cells with were pretreated with different concentrations of gemfibrozil and H2O2, concomitantly. Results: In gemfibrozil pretreated groups, reduced level of caspase-3 and raised mitochondrial transcription factor A (TFAM) levels were detected. In contrast, adding fulvestrant, an Estradiol receptor antagonist, prevents the impact of gemfibrozil on oxidative stress condition, reducing its efficacy to protect the neurons against stress. Conclusion: Our results indicated the involvement of estradiol receptors in gemfibrozil neuroprotective mechanism, in diminishing oxidative stress-induced damage via reducing caspase-3 and inducing the level of TFAM that plays a crucial role in the mitochondrial biogenesis.}, Keywords = {Gemfibrozil, Mitochondrial transcription factor A, Fulvestrant, Caspase 3, H2O2 }, volume = {19}, Number = {4}, pages = {253-262}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1129-en.html}, eprint = {http://ppj.phypha.ir/article-1-1129-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Salihi, Abbas BQ}, title = {Activation of Inward Rectifier Potassium Channels in High Salt Impairment of Hydrogen Sulfide-Induced Aortic Relaxation in Rats}, abstract ={Introduction: Hydrogen sulfide (H2S) plays a key role in the regulation of vascular tone and protection of blood vessels against endothelial dysfunction. Since the mechanism of salt impairing H2S-induced vascular relaxation is not fully clear, therefore this study was designed to investigate the role of potassium (K+) channels in the vasodilatory effects of exogenous H2S in rat aortic rings. Materials and Methods: Isolated thoracic aortic rings of adult male albino rats fed 8% NaCl diet for six weeks were used for isometric tension recording using PowerLab tissue bath system. Results: The relaxation response to sodium disulfide (Na2S, an H2S donor) was reduced in aortic rings of rats that were either fed high salt (HS) or incubated in a medium containing 1,3 or 5mM/L of extra NaCl compared with control rings. Na2S-induced relaxation was lower in rings precontracted by high K+ than phenylephrine (PE, a selective α1adrenergic receptor agonist). In addition, incubation of aortic rings of HS loaded rats with inward-rectifier K+ (KIR) channels blocker individually or simultaneously with either ATP-dependent (KATP) or voltage-sensitive K+ (KV) channels blockers inhibited Na2S-induced relaxation in PE-precontracted rings; however it had no effects on rings pretreated with KATP channels blocker. In contrast, incubation of aortic rings of HS loaded rats with Ca+2 activated K+ (KCa) channels blocker individually or in combination with KIR channels blocker significantly enhanced Na2S-induced relaxation. Conclusion: These results revealed that HS partially impairs aortic relaxation caused by H2S, and that the mechanism of relaxation is mainly mediated by the stimulation of KIR channels and inhibition of KCa channels.}, Keywords = {Hydrogen sulfide, KIR channels, Relaxation, Aorta, High-salt diet}, volume = {19}, Number = {4}, pages = {263-273}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1137-en.html}, eprint = {http://ppj.phypha.ir/article-1-1137-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} } @article{ author = {Kamali, Mahboubeh and Sahraei, Hedayat and Khosravi, Maryam and Hassanpour, Shahin and Yaribeygi, Habib}, title = {Asymmetric Involvement of Central and the Peripheral NMDA Glutamate Receptors in the Expression of Withdrawal Syndrome in Morphine-Dependent Mice}, abstract ={Introduction: Morphine withdrawal syndrome is mediated via several central and peripheral neurological pathways. In the present study we investigated the role of N-methyl-D aspartic acid (NMDA) glutamate receptor on naloxone-induced withdrawal syndrome in morphine-conditioned mice. Materials and Methods: We designed two separate experiments. In experiment one, 30 male NMRI mice were divided into 5 groups, pretreated with memantine (0.1, 1 and 5 mg/kg; I.P.) followed by morphine-dependence period for 3 days. In the other experiment, 48 male NMRI mice distributed into 8 groups, pretreated with intra-accumbens (IAc) memantine (1 and 5 μg/animal) within the right, left and both side of nucleus accumbens (RNAcc, LNAcc and BNAcc) followed by I.P. morphine-dependence (3 days). On day 4, in both experiments, morphine was injected into mice, followed by naloxone. Then naloxone-induced total jumping count, jump height and defecation in morphine-conditioned mice were recorded for 30 min. Results: Pre-treatment by I.P. injection of memantine significantly attenuated naloxone precipitated jumping count/30 min, jumping height (mm) and fecal material output in morphine dependent mice (P<0.05). Also, IAC pretreatment with memantine in LNAcc, RNAcc and BNAcc significantly declined the effect of I.P. injection of naloxone on total jumping count and jumping height (P<0.05), pretreatment within memantine in LNAcc, RNAcc and BNAcc had no effect on defecation (P>0.05). Conclusion: These findings indicated asymmetric involvement of central and peripheral NMDA glutamate receptors in withdrawal syndrome development in morphine-dependent mice.}, Keywords = {Memantine, NMDA glutamate receptors, Morphine withdrawal syndrome, Mice}, volume = {19}, Number = {4}, pages = {274-284}, publisher = {Iranian Society of Physiology and Pharmacology}, url = {http://ppj.phypha.ir/article-1-1134-en.html}, eprint = {http://ppj.phypha.ir/article-1-1134-en.pdf}, journal = {Physiology and Pharmacology}, issn = {24765236}, eissn = {24765244}, year = {2015} }