Physiology and Pharmacology
Volume:15 Issue: 3, 2012

The aim of the present study was to determine direct effects of NO modulation on protective electrophysiological properties of atrioventricular node (AV node) in the experimental model of AF in rabbit. Isolated perfused rabbit AV nodal preparations were used in two groups. In the first group (N=7), LNAME (50μM) was applied. In the second group (N=12), different concentrations of L - argenine (250 μM - 5000 μM) were added to the solution. Programmed stimulation protocols were used to quantify AV nodal conduction time, refractoriness and zone of concealment. AF protocol was executed by software with coupling intervals (ranging from 75 – 125 msec). L-NAME had depressive effects on basic AV nodal properties. L-Arginine (250μM) had direct inhibitory effects on nodal conduction time, Wenckebach and refractoriness. Significant increases in the number of concealed beats were induced by L-Arginine (500 μM). Number of concealed beats were increased from 700.7 ± 33.7 to 763 ±21 msec (P<0.05). Trend of zone of concealment prolongation in a frequency-dependent model was abrogated by Larginine (250, 5000 μM). NO at low concentration (in the presence of L-NAME) had facilitatory role on AV nodal properties, but at high concentration (in the presence of L-arginine) enhanced protective role of AV node during AF. Biphasic modulatory role of NO may affect protective behavior of AV node during AF.

In this study, the effect of para-nonylphenol as an environmental pollutant on viability, morphology and proliferation of bone marrow mesenchymal stem cells was investigated. Bone marrow mesenchymal stem cells of rat were treated with the 0.5, 1, 2.5, 3.5 and 5 μM of paranonylphenol for a period of 21 days, then the viability of the cells were estimated using trypan blue and MTT methods. After choosing the effective dose, the integration of the DNA was investigated using comet assay and agarose gel electrophoresis. Mechanisms of cell death were also investigated by TUNEL assay and presence of caspase activity. The results showed that para-nonylphenol caused significant dose dependent reduction of viability and proliferation of the cells. Comet assay, agarose gel electrophoresis and TUNEL test showed that the DNA of the cells were damaged and broken after treatment with 0.5 and 2.5 μM of para-nonylphenol. In addition, activated caspase-3 was observed in the cytoplasm of treated cells. This study showed that a very low concentration of para-nonylphenol has drastic effects on bone marrow mesenchymal stem cells. This chemical is used in formulation of cosmetics and detergents and therfore may have detrimental effects on the viability and proliferation of stem cells.

Response to morphine and role of Nitric Oxide (NO) on expression of morphine response has been studied in vertebrates. But, little evidence is provided in the matter in earlier invertebrates. This investigation for the first time evaluated the effect of NO on expression of morphine potency in Paramecium caudatum.

Animal after isolation from natural media and specific identification was cultured in laboratory. 1 ml of the isolated medium including the animals was added into the Sedgwick– Rafter cell counter. One μl of drugs was infused into the cell counter. Morphine (1-60 μg/μl) was infused into the cell and its effect was recorded throughout 0- 180 sec. L-Arginine (1-8 μg/μl), a NO precursor, was infused prior to morphine (2 μg/μl). The NO producing enzyme was inhibited by preinfusion of L-NAME. Also the naloxone was used to show the involvement of the opioid receptors in the signaling of morphine response. In control speciements distilled water was added solely.

The Paramecia under the infusion of morphine were aggregated. The most aggregation rate was observed at a relatively low dose of the drug (2 μg/μl). L-Arginine showed a positive effect on the response (p<0.001) whearas the effect was blocked by preinfusion of the L- NAME. Naloxone showed an inhibitory effect to morphine response. The activity of the NOS was shown by using the NADPH-diaphorase.

A sign of morphine potency in single–celled animal is the cell aggregation, and the present results are showing the interaction of NO system with the opioidergic system in this line. On the other hand, concerning the potentiation effect of L-arginine on morphine effective dose in the model, this finding may be useful in reducing of morphine’s side effects in patients under the treatment of the drug, and in the drug economy as well.

The effect of regular exercise in decreasing the incidence of heart diseases is well known. The abuse of anabolic androgenic steroids (AAS) has been associated with cardiovascular disorders. Uncoupling proteins (UCPs) transport protons across the inner mitochondrial membrane; thereby proton gradient can be diminished by the action of UCPs. This process will result in the uncoupling of mitochondrial respiration from ATP production. The goal of this study was to investigate whether UCP2 and UCP3 are involved in the mechanisms of AAS-induced cardiac damage in the rat heart. In the current study, adult male Wistar rats were divided into five groups (n=8): Control, vehicle, nandrolone, exercise, exercise- nandrolone. Rats in the exercise groups were submitted to a progressive running program on a treadmill, 5 days a week for 10 weeks. Rats in the nandrolone and exercise- nandrolone groups received a weekly intramuscular injection of nandrolone decanoate (10 mg/kg), while those in the vehicle group received Arachiz oil as vehicle. Relative mRNA expression of UCP2 and UCP3 were determined with real-time RT- PCR. The data showed that chronic administration of nandrolone significantly up-regulated UCP2 and UCP3 mRNA in rat heart and endurance training induced a decrease in the expression of UCP2 and UCP3 mRNA with or without presence of nandrolone. It may be concluded that chronic nandrolone treatment causes an increase in the expression of UCP2 and UCP3 mRNA. Thus, it might decrease energy metabolism efficiency by impairment of ATP production. Physical activity may decrease the adverse effects of nandrolone by down-regulation of the UCP2 and UCP3 mRNA expression.

It was shown in a previous study, that MCPIP, a cilostamide derivative, increased atrial contraction force without changing contraction rate. To improve this property, two new derivatives of cilostamide were synthesized and their effects on PDE3 activity and isolated rat atria contraction were investigated. The inhibitory effect of each compound on PDE3 enzyme was determined. Reserpine-treated rat atria were separated and suspended in an organ bath containing Krebs-Henseleit buffer. The effects of each compound alone or in combination with isoprenaline were assessed. Mc2 and mbc2 inhibited PDE3 activity with a potency lower than cilostamide, while they increased the contraction force with a higher efficacy (percentage higher than base line, cilostamide=19±3%, P<0.05, mc2= 43±7% and mbc2=34±5%, P<0.001). The effect of isoprenaline was potentiated by cilostamide and new compounds with different efficacies (mc2>mbc2>cilostamide). Atrial contraction rate was increased in the presence of cilostamide or isoprenaline, but was not changed with synthetic compounds. Furthermore, the effect of isoprenaline on the contraction rate was inhibited by synthetic compounds (percentage higher than base line, isoprenaline=68±9%, +mc2=6±5% and +mbc2=36±6%) and was not changed in the presence of cilostamide. The synthetic compounds induced an increase in the atrial contraction force that was higher than cilostamide and was not correlated to their PDE3 inhibition. These compounds potentiated the effect of isoprenaline on the contraction force which excludes the possibility of their inhibitory effect on the receptor. In addition to PDE3 inhibition, other mechanisms are involved in producing the effects of these compounds, which are not clear and needs further investigation.

Cyclophosphamide (CP) is used for the treatment of various cancers. In spite of its therapeutic importance, a wide range of adverse effects such as reproductive toxicity has been observed following the administration of this drug in human and experimental animals. In the current study, we have investigated the adverse effects of CP on morphology and histology of testis rats. Twenty-one male Wistar rats were selected and randomly divided into 3 groups. CP was used at a dose of 6.1 mg/kg/day, (i.p.) for 50 days. At the end of the treatment, the histological and biochemical changes in testis, as well as sperm count and motility were assessed. Testicular weight, sperm count and motility as well as serum testosterone concentration were significantly decreased whereas malondialdehyde (MDA) level was significantly increased in CP group compared with those in the control and sham groups. In addition, histological studies of testis structure showed that seminiferous tubules of testis were severely damaged in the CP group. CP increased the number of sloughing tubules and interstitial space, while it decreased seminiferous tubular diameter (STD), seminiferous epithelial height (SE), tubule differentiation index (TDI) and spermiation index (SPI). The results suggest that cyclophosphamide affect fertility parameters and cause testis atrophy after chronic treatment.

Considering the long traditional history of anti-inflammatory and anti-spasmodic effects of Matricria spices on the gastrointestinal system, the present study aimed to investigate the role of calcium channels and Histamine receptors in the inhibitory effects of hydroalcoholic dry extract of German chamomile (Matricaria recutita L.) on the isolated rabbit jejunum. All experiments were done on the isolated jejunum of New Zealand rabbits (1.8-2.5 kg). Dry extract of aerial parts of M. recutita was obtained by the maceration technique. The study was performed on two groups (n=6 in each group). In the first group, the effects of cumulative concentrations of M. recutita (3×10-3-1×10-2 mg/ml) on normal and K+-induced contractions (50 mM) of isolated jejunum were studied. In the second group, the inhibitory role of M. recutita (3 – 13×10-3 mg/ml) was evaluated in the presence and absence of histamine and cetrizine. In the presence and absence of 10 μM certizine, a histamine H1-antagonist, a concentration-dependent inhibitory effect of M. recutita extract in the range of 3-13×10-3 mg/ml was recorded the rabbit jejunum. Results showed that EC50 of M. recutita in the absence and presence of K+ was 6.3×10-3 and 6.5×10- 3mg/ml, respectively. IC50 values for two concentrations of M. recutita (8×10-3, 1×10-2) to abrogated contractive phase of Histamine was 9.55 × 10-6 and 1.57 × 10-6 μM. Cetrizine (10 μM) abolished inhibitory effects of M. recutita (IC50=3.6×10-3), (p< 0.001). Dry extract of matricaria recutita had inhibitory effects on the contractions of isolated rabbit jejunum. Calcium channels and histamine were involved in these antispasmodic effects

The antinociceptive effect of morphine is, in part, mediated through the activation of a descending pathway. One of the major components of this pathway is the nucleus raphe magnus (NRM). Our previous study demonstrated the involvement of NRM in the analgesic effect of morphine microinjected into the nucleus cuneiformis (NCF) in a descending manner. The aim of the current study was to investigate another aspect of the interaction between these two nuclei in both acute and chronic inflammatory pain models. In order to calculate 50% effective dose (ED50) of morphine, animals received bilateral morphine injections (1, 2.5, 5 and 10 μg/0.5 μl saline) into the NRM. The obtained ED50 of morphine was applied into the NRM with/without bilateral electrolytic lesion (500 μA, 30 sec) of the NCF. Tail-flick and formalin tests were applied as behavioral analgesic tests in this study. Results interestingly showed that the intra-NRM morphine injection (ED50; 1 μg/0.5 μl saline) resulted in an increase in tail flick latencies (morphine-induced antinociception) at 30-min intervals, while bilateral electrolytic lesions in the NCF could notably decreased the morphine-induced antinociception during 30-90 min after the injection of morphine. Data also showed that bilateral morphine microinjected into the NRM, dose-dependently increases the antinociceptive responses during both early and late phases of formalin test. The antinociceptive effect of morphine microinjected into the NRM was significantly attenuated at the late phase but not early phase following the bilateral destruction of NCF in formalin test. It could be concluded that there is a reciprocal interaction between NRM and NCF during morphine - induced antinociception in both acute and chronic inflammatory pain models in rat.

Nitric Oxide is an important endogenous compound that acts as bronchodilator in trachea. Electromagnetic fields (EMF) affect nitric oxide level in different tissues. The interaction of nitrergic and cholinergic systems in airways has been reported. Therefore, the present study was performed to evaluate the interaction of cholinergic and nitrergic systems in the trachea of rats that have been exposed to EMF. Adult male rats were divided into 3 groups: experimental group was exposed to 1 mT (militesla) EMF for 135 days, sham group was kept in the same condition but in off solenoid and control group was kept in normal condition. After 135 days, the mechanical response of transverse rings of isolated trachea to acetylcholine in the absence and presence of L-NAME, an inhibitor of nitric oxide synthesis, were recorded using PowerLab-AD system. The results showed a significant increase in cholinergic contractions of trachea in the presence of L-NAME in control and sham groups (P< 0.05). However this enhancement of contraction was not detected in EMF exposed group. It can be concluded that nitric oxide has a modulatory effect on the airway cholinergic contraction, however this modulation is inhibited by prolonged exposure to EMF.

It is known that acute and chronic stress induce hormonal and neuronal changes which affecting both pain threshold and nociceptive behaviours. Orexin plays an important role in modulation of pain and stress. Considering pain modulation during stress and the role of orexin in pain and stress, orexin might be involved in pain modulation during stress.We evaluated the involvement of orexin receptor-1in acute immobilization stress on the tonic pain model. Adult male, Wistar rats (200–300 g), placed in a stereotaxic apparatus and canulla were inserted into their left cerebral ventricle. After 1 week of recovery, animals were initially submitted to one session of acute restraint stress (30 min) and immediately submitted to formalin injection in the hind paw to evaluate nociceptive behaviours. Orexin receptor 1 antagonist (SB 334867) was injected intracerebroventricularly, 5 minute before formalin injection, while the solvent was injected in the control group. two percent formalin produced typical biphasic pain responses in rats that was observed for more than 1 hour. Acute exposure to restraint stress reduced the nociceptive behaviour by chemical stimulation in phase 1, interphase and phase 2. The short-term stress induced analgesia was reflected in a decrease in the nociceptive behaviour during phase 1, whereas the long-term stress induced analgesia was reflected in a decrease in the nociceptive behaviours during phase 2. Pretreatment with orexin receptor 1 antagonist (SB 334867) attenuated the antinociceptive behavioral effect of restraint stress. Our results indicate that orexin receptor 1 antagonist attenuated antinociceptive effect of restraint stress assessed by formalin. These findings show that orexin receptor 1 might mediate an opioid-independent stress-induced analgesia.

Boron possesses widespread properties and is important for human and animal nutrition. Since Boron is rapidly bioavailable, the objective of the present study was to determine whether acute (hourly or daily), and weekly supplementationcould have any significant biological effects on the synthesis of steroids as well as inflammatory biomarkers. Eight male volunteers participated in experiments on three occasions (day 0, 1 and 7). On the first day (day 0), a blood sample was collected at 8.00 A. M, followed by ingestion of placebo. On the next day (supplementation- day 1), similar procedure was followed by ingestion of 10 mg of boron capsule. On both occasions samples of blood were collected every 2h for the next 6 h. Subjects consumed a capsule of 10 mg boron every day and on day 7, blood collection was carried out again at 8.00 A.M. Independent sample t-tests were used to evaluate the differences. Plasma boron was significantly increasedfollowing hourly (P=0.002) and weekly (P=0.000) consumption of boron. After one week of supplementation, free testosterone levels were significantly increased (P<= 0.02) and estradiol concentrations were significantly decreased (P<= 0.01). Dihydrotestosterone (DHT), cortisol and Vitamin D showed slight non significant, increases. The ratios of free testosterone/testosterone (FT/T) (P<= 0.001), free testosterone/estradiol (FT/E2) (P<= 0.004) and testosterone/estradiol (T/E2) (P<= 0.009) were significantly increased. Also, all 3 inflammatory biomarkers were decreased after supplementation. Although there are previous studies that report a decrease in proinflammatory cytokines induced by boron consumption, to our knowledge, this is the first human study reporting an increase in plasma free testosterone concentrations following consumption of a boron supplement. This indicates a possible protective role against diseases of pathological conditions for this microelement.

Perepubertal varicocele can result in hypotrophy of testes, sperm damage and decrease the function of leydig cells in future. pathophysiology of varicocele is unclear. Increased reactive oxygen species (ROS) is a major theory. There are many controversies in treatment of pediatric varicocele. Flaxseed (FS) is the richest source of lignans with antioxidant properties. The aim of this study was to investigate effect of flaxseed on oxidative stress in prepubertal rats with experimental varicocele. 35 male prepubertal rats were divided into 5 groups: control, sham, sham that fed base diet which was supplemented with 10% FS, varicocele, varicocele that fed base diet which was supplemented with 10% FS. Animals were sacrificed six weeks later. Sperm superoxide anion and H2O2 production, MDA in testis and total antioxidant capacity in semen were evaluated. Intracellular superoxide anion and H2O2 production was significantly higher in varicocele induced group (P≤0.001), but FS significantly decreased them (P≤0.001). There was no significant difference for seminal plasma total antioxidant activity among all groups (P≥0.05). Left testicular MDA concentration of rats with varicocele that were fed by FS 10% was lower compared with varicocele groups (P≤0.05). Fs as a fat soluble antioxidant can protect the sperm membrane from the damage induced by ROS through its effective antioxidant potential.

The principal dose-limiting factor in the use of cisplatin as an antineoplastic drug is its hepatic toxicity. This study was designed to investigate the protective role of taurine against cisplatin-induced hepatic injury. Male albino rats (180-220 g) were divided in to 4 groups (n=8) as follows: (1) saline-treated group (2): cisplatin-treated group (10 mg/kg ip) (3): group that received taurine (200 mg/kg ip) for 1hr before cisplatin (10 mg/kg ip) administration (4): taurine treated group (200 mg/kg ip). After 7 days, the animals were sacrificed and blood samples collected from the heart as well as liver tissues were kept at -70 °C till further analyses. analyses showed that cisplatin significantly increased ALT and AST serum levels (P<0.05) while pretreatment with taurine resulted in the reduction of these markers. Catalase activity in cisplatin-treated rats was significantly decreased (P<0.05) and taurine administration could recover this reduction. MDA content of the liver tissue was significantly increased in cisplatin-exposed animals, while taurine treatment reduced the amount of MDA in liver tissue. Our data suggest that taurine prevents from cisplatin-induced hepatic injury and this effect may be due to its antioxidant properties.

Nitric oxide (NO) is a neuronal messenger molecule in the central nervous system, which is generated from L-arginine by nitric oxide synthase (NOS) and involves in many important opioid-induced effects. Our previous studies revealed that Cuminum cyminum interestingly reduces morphine sensitization, tolerance and dependency in male mice. Therefore, in the present study, the effect of intraperitoneal (ip) administration of different doses of cumin fruit essential oil (FEO) on the acquisition of morphine-induced conditioned place preference (CPP) in L-arginine treated mice was investigated. In this study, the CPP paradigm was done on 231 adult male albino Wistar mice and conditioning scores and locomotor activity were recorded by the Ethovision software. The results showed that solely administration of different doses of cumin FEO (0.01, 0.1, 0.5, 1 and 2%; ip) or L-arginine (50, 100 and 200 mg/kg; ip) during CPP protocol could not induce CPP. Nonetheless, morphineinduced CPP was significantly decreased by two higher doses of cumin FEO (1% and 2%; P<0.05), while it was increased by L-arginine (100 and 200 mg/kg) when they were injected before morphine (5 mg/kg) during the acquisition period (P<0.001). Additionally, cumin FEO (0.01-2%) could interestingly attenuate the increasing effect of L-arginine (200 mg/kg) on morphine-induced CPP in a dose-dependent manner. In conclusion, it could be suggested that some components of cumin FEO attenuate the excessive effect of L-arginine on morphine-induced CPP through inhibitory mechanisms on NO pathway. It seems that cumin FEO possibly acts as a NOS inhibitor.

Dracocephalum polychaetum bornum is exclusively found in a limited geographical area in the Kerman province; It is used by the local people for treatment of abdominal pain, meteorism and musculoskeletal pain. No study has been performed on the effects of D. polychaetum bornum, so the aim of this work was to assess the role of the extract and essential oil of this plant on pain and anxiety assessed by formalin test and elevated plus-maze (EPM), respectively, in male rats. Analgesic effects: One hundred twelve NMRI male rats were divided into 14 groups. Aqueous extract and essential oil were administered to 8 groups at doses of 25, 50, 100 and 200 mg/kg i.p., while 2 groups were treated with normal saline, and the last 4 groups (sham positive) received ASA (300 mg/kg) and morphine (2.5 mg/kg). Anxiolytic effect: Forty-two NMRI male rats were divided into 7 groups. Four groups were injected intraperitoneally with 25, 50, 100 and 200 mg/kg of the extract of the plant and 2 groups were injected with normal saline (control group) and 1 mg/kg diazepam (positive sham). Anxiolytic effect was evaluated by EPM. The results showed that the extract but not the essential oil at the dose of 200 mg/kg had a significant analgesic effect 25, 30 and 35 minutes after administration. The findings on the anxiolytic effect revealed that there was no significant difference between groups treated with different doses. This study showed that D. polychaetum bornum had analgesic effects.