Physiology and Pharmacology
Year:2013 | Volume:17 | Issue:2|Papers Count:15

Introduction: Cardiac preconditioning is an important method to reduce the damage caused by prolonged ischemia.Previous studies have shown that corticosteroids have protective effects on the heart, however at high concentrations this effect may be reduced with unknown mechanisms. We hypothesize that the contradictory effects of hydrocortisone at high concentration may be mediated via mineralocorticoid receptors. Therefore, this study was designed to determine the protective effects of various concentrations of hydrocortisone on the heart and its relationship with the mineralocorticoid receptor.Methods: In an experimental study, ninety-six male rats were divided into eight groups treated with different doses of hydrocortisone (1, 5, 10 and 20 mM). Spirinolactone was used as a mineralocorticoid receptor antagonist to investigate its role in the hydrocortisone acute effects on the heart. The hearts were excised first, and transferred and connected to the Langendorff system, and then subjected to 30 min ischemia and 90 min reperfusion. The infarct size and ventricular arrhythmias were measured. Two-way ANOVA was used to compare the groups.Results: The results showed that hydrocortisone at various concentrations could reduce the infarct size and protect cardiomyocytes. The protective effects were lower at high concentrations (P<0.05). Spironolactone, a mineralocorticoid receptor antagonist amplified these protective effects (P<0.05). Hydrocortisone and spironolactone administration not significantly decreased severity and incidence of ventricular arrhythmia in comparison with IR group (P>0.05).Conclusion: The results showed the hydrocortisone cardioprotective effects as a pharmacological preconditioning agent. Opposing effects of hydrocortisone at medium and high concentrations can at least be partially reversed by mineralocorticoid receptors.

Introduction: Reactive oxygen species (ROS) have been suggested to play an important role in the myocardial damage induced by ischemia-reperfusion. One element believed to be activated by ROS and to contribute to the reduction of ROS production, is the uncoupling protein-2 (UCP2). The objective of this investigation was to explore the effect of myocardial ischemia reperfusion on cardiac UCP2 mRNA and protein levels.Methods: Male Wistar rats (250-300gr) were subjected to 30 min occlusion and 2 hours reperfusion of left coronary artery. The expression of UCP2 mRNA and protein in the ischemic area of left ventricle and non ischemic area from right ventricle were analyzed. The mRNA and protein expression were determined by RT-PCR and western blotting, respectively.Results: Compared to control hearts, exposure to myocardial ischemia reperfusion caused a significant increase in UCP2 protein in the ischemic area of the left ventricle (116%±18, P<0.001), however UCP2 mRNA expression did not change significantly. Furthermore, in the non ischemic area of the right ventricle, neither protein nor mRNA levels were affected by myocardial ischemia reperfusion.Conclusion: We conclude that following acute myocardial ischemia reperfusion, UCP2 protein level is increased in the ischemic area of the left ventricle but not in the non ischemic area of the right ventricle, suggesting the local effect of ischemia on UCP2 protein expression. Furthermore, the discordance between mRNA and protein expression of UCP2 suggests that post transcriptional regulation of mRNA influences protein induction.

Introduction: Amniotic membrane, the innermost layer of extra-embryonic tissue, contains mesenchymal and epithelial stem cells. The amniotic mesenchymal cells have the capability of inhibition of growth of cancer cells. In this research, the effects of amniotic epithelial cells on the viability of cancer cells and the role of apoptosis in this procedure were evaluated.Methods: Amniotic membrane derived epithelial cells were cultured for 24 hours and their supernatant was added to the culture of cancer cells (HeLa and MDA-MB-231) in volumes of 200, 400, 600 and 800 ml. Viability of cancer cell lines were measured by MTT assay after 24 hours. Also, the expression of caspase 3 and 8 (pro apoptotic proteins) was evaluated with immunocytochemistry. Analysis of data was performed using one-way analysis and post-Tukey test in ANOVA.Results: Viability of cancer cells were significantly decreased after culture with condition medium of amniotic epithelial cells in comparison to the control group. This decrease was dose-dependent and more significant at higher doses (600 and 800 ml). The expression of caspase-3 and caspase-8 was dose-dependently increased in cancer cells.Conclusion: The promising results of this study showed that amniotic epithelial cells have the capability to be investigated as a proper candidate for cancer therapy.

Introduction: Uncoupling protein 2 (UCP2) in the inner mitochondrial membrane changes the activity of KATP channels and the cell excitability, probably by decreasing the ATP production. Given the expression of UCP2 in primary afferent neurons, and the importance of these channels in morphine-induced analgesia, genipin, an UCP2 inhibitor, may affect these processes, when administrated intrathecally.Methods: Tail flick assay and formalin test were used to study thermal and chemical pain, respectively, in adult male Wistar rats. Catheterization of the spinal subarachnoid space was used to localize the effects of genipin.Results: Genipin increased pain sensation in tail flick assay and in the first phase of the formalin test, but decreased pain in the second phase of the formalin test (P<0.001 in all groups). Genipin also antagonized analgesic effect of morphine (P<0.01 in tail flick and P<0.001 in the first phase of the formalin test) and did potentiate it in the second phase of the formalin test (P<0.001); but had no effect on hyperalgesic effects of ultra-low dose of morphine.Conclusion: Probably, genipin increases ATP/ADP ratio, thereby inhibits KATP channels in primary pain afferents and lowers pain threshold and decreases analgesic effects of morphine, at least in part, by inhibition of UCP2.Apparently, the anti-inflammatory effect of genipin causes analgesia in the formalin test. Genipin had no effect on hyperalgesic effects of ultra-low dose of morphine, maybe due to the common signaling mechanisms such as KATP channels.

Introduction: Oxidative stress is the result of imbalance between free radicals and the antioxidant defense mechanisms of the body. Oxidative stress in brain causes dysfunction of brain activities, destruction of neurons, and disorders like Alzheimer disease. In this experimental study, we examined the protective effect of Salvia officinalis L. against oxidative stress induced by intracerebroventricular injection of streptozotocin in male rats.Methods: In the experimental research, Wistar rats were divided into control, sham, and experimental groups.Experimental groups received 25, 50 and 100 mg/kg body weight of hydroalcoholic extract of Salvia officinalis intraperitoneally. After two weeks, surgical procedure was performed on sham and experimental groups and after one week of recovery, streptozotocin was injected intracerebroventricularly (i.c.v-STZ) at 3 mg/kg. Brain hemispheres were separated after four weeks. Finally, superoxide dismutase (SOD) and catalase (CAT) levels were measured in brain hemispheres.Results: In the group receiving STZ, CAT and SOD levels were significantly decreased compared to the control group (P<0.001), whereas intraperitoneal injection of different doses of Salvia officinalis leaves extract significantly increased SOD and CAT levels compared to STZ group (P<0.001).Conclusion: These data show that antioxidant effects of Salvia officinalis L. could prevent oxidative stress induced by i.c.v.-STZ injection in the brains of male rats.

Introduction: Skeletal muscle is a flexible and ever changing tissue and the role of costameric proteins in its response to different stimuli is not well defined. The aim of this study was to investigate the effect of progressive resistance exercise on b1 integrin and vinculin proteins in fast and slow twitch skeletal muscles of male rats.Methods: Twelve male Wistar rats (weight: 298±5.2 gr; age: 3 months) were randomly assigned into trained (n=6) and control (n=6) groups after a period of two weeks of inhabitation. In the beginning of the third week, progressiveresistance exercise protocol (to climb up of one meter ladder, 3 sets, 10 repetitions in each set, at 50%, 75%, and 100% of their own body weight) was performed. The control group did not perform any exercise activity. Twelve hours after the last session of acute exercise, rats (control and trained) were sacrificed and their slow-and fast-twitch muscles) Soleus and Flexor hallucis longus) were collected. An ELISA assay was used to determine alterations occurred in the levels of b1 integrin and vinculin proteins. Statistical analyses were made with independent t tests.Results: The results showed that there was no significant change in b1 integrin levels of fast-twitch muscle and vinculin levels of slow-and fast-twitch muscles (p≥0.05). However, a significant change was detected in b1 integrin level in the slow-twitch muscle (p≤0.05).Conclusion: Since that costameric proteins contribute to the maintenance of the structure and stability of muscles and also have a role in the cell signaling, therefore, resistance exercise can be an effective stimulus in improving slowtwitch muscles for stabilization of the muscle structure.

Introduction: Cyclophosphamide (CYP) is an alkylating agent, which is used in different diseases. It has several important side effects on ovaries.Tribulus terrestris extract (TTE) has different steroidal saponins and has been used for a long time as an aphrodisiac. The aim of this study was to evaluate the protective effects of TTE on the toxicity of CYP in the ovary of rats.Methods: Forty-eight female rats were divided into 6 groups. First group received only normal saline. Group 2, 3 and 5 received CYP (30 mg/kg, 2 times/week for 7 weeks). Groups 3 and 4 received TTE (10 mg/kg, 2 times/week for 10 weeks) and groups 5 and 6 received vitamin C (80 mg/kg, 2 times/week for 7 weeks). At the end of study, blood was collected and the rats were sacrificed. Ovaries were dissected for the histopathological study. Serum levels of estrogen were measured.Results: Histopathological examination revealed significant decrease in the number of follicles in group 2. Estrogen was significantly decreased by CYP in comparison with other groups. Number of follicles in group 3 and 5 were increased. Estrogen levels were also increased.Conclusion: These findings indicated that TTE similar to Vitamin C may improve the side effects of CYP toxicity in the ovary of rats.

Introduction: With the increasing development of nanotechnology, nanomaterials are used instead of conventional compounds. One of these nanomaterials that have many applications in the biomedical field, is iron oxide (Fe2O3) nanoparticles and there is not much research on its effects on the physiological features. So in this research, effect of iron oxide nanoparticles on short and long-term passive avoidance memory and levels of serotonin and dopamine in hippocampus was evaluated in comparison to the bulk type.Methods: In this study, 80 male adult Wistar rats (220±30grams) were used and divided into 10 groups, and the study was performed in two parts in order to measure the behavioral changes and neurotransmitters levels. In the first part, animals received intraperitoneal injections of iron oxide nanoparticles and bulk at different doses (0.2, 1, 5 mg/kg (before training. Then, 90 minutes and 24 hours after training their memory was tested by a step-through instrument. In the second part of the study, right and left hippocampi of every group were extracted after receiving the effective dose (5 mg/kg) of iron oxide nanoparticles and bulk, and neurotransmitters levels were measured by an ELISA kit.Results: Iron oxide nanoparticles caused a disruption in passive avoidance memory in a dose-dependent manner, while bulk iron oxide showed a non significant partial effect. Also both type of iron oxide reduced dopamine levels and increased serotonin levels significantly or relatively in both hippocampi.Conclusion: It seems that iron oxide nanoparticles induce a disruption of memory, which is in part related to the alterations of neurotransmitters levels in hypocampus and the other is associated to its physicochemical properties.

Introduction: Thymol has negative ionotropic effect on heart and has direct effect on calcium release from sarcoplasmic reticulum. Some of the herbal plants just like carum copticum consist of thymol. The postganglionic neurons of the gastrointestinal parasympathetic system are located mainly in the myenteric and submucosal plexuses.Stimulation of these parasympathetic nerves causes general increase in activity of the entire enteric nervous system. This in turn enhances activity of most gastrointestinal functions. Therefore the present study has been designed to find out the anti spasmodic effects of thymol on rat’s ileum smooth muscle.Methods: In this study rat’s ileum contraction was recorded through an isolated tissue chamber in an organ bath by using isotonic transducer and oscillographic device and in each experiment the effective concentration of Carum Copticum and thyme essential oil (0.002, 0.005 and 0.01) on acetylcholine induced contraction in isolated rat’s ileum was evaluated and compared with thymol (10-3, 10 -4 and 10 -5) effects.Results: Our result show that acetylcholine in the presence of thymol with concentration of 10-4 & 10-5 M cause smooth muscle contraction while its concentration of 10-3 M inhibited smooth muscle contraction which is significant as compared with control group (P<0.05).Conclusion: this study showed that thymol inhibited acetylcholine induced contraction in isolated rat’s ileum and due to the high concentration in some of medicinal plant; its anti spasmodic effects may be due to the presence of thymol on that.

Introduction: In the Iranian traditional medicine, Ziziphus jujuba is recommended for treatment of anemia, but no investigation has addressed this issue. In the present study, the effect of hydro-alcoholic extract of this plant was evaluated on the peripheral blood cells in male Balb/c mice.Methods: Hydro-alcoholic extract was prepared from the fruits of the Ziziphus jujuba. Male mice were injected with normal saline or the extract (100, 200 or 400 mg/kg, i.p.) for a period of two weeks. Afterwards, the mice were anesthetized and blood samples were taken from their hearts and then the peripheral blood was evaluated by a Cell Counter apparatus. White blood cells differential analysis was manually performed under a microscope. Data was statistically analyzed using One-way ANOVA followed by Tukey post-hoc test.Results: Ziziphus jujuba extracts (100 and 400 mg/kg) caused a significant reduction in the percentages of monocytes and neutrophils, respectively (P<0.05). At a dose of 400 mg/kg, Ziziphus jujuba extract increased the percentage of lymphocytes (P<0.05). However, no significant changes were observed in the amounts of WBC, RBC, platelets, hemoglobin, Hct, MCV, MCH and MCHC in the extract-treated groups (P>0.05).Conclusion: Findings of this study show that Ziziphus jujuba extract increases the percentage of lymphocytes and also reduces the percentage of monocytes and neutrophils.

Introduction: Rosa Damasca essential oil is currently used as anti-depressant in animal models and human. Considering the similarities betweenRosa Canina and Rosa Damasca, the effects of water and alcoholic extracts of R. Caninaon depression induced by forced swimming test (FST) in mice were investigated.Methods: Male NMRI mice (25-30 g) were used (n=6/group). Intraperitoneal injections of alcoholic (5, 10, 20, 30, and 40 mg/kg) and/or water (10, 20 and 30 mg/kg) extracts were administered to the animals 30 min before the FS.Intracerebroventricular injections of the alcoholic and water extracts (1, 5 and 10 mg/mice) to the animals were performed 5 min before FST.Results: Both intraperitoneal (20 and 30 mg/kg) and intracerebroventricular (5, 10 mg/Mouse) injections of R.CaninaL. water extract dose-dependently reduced the animals immobilization, which was similar to the fluoxetine effect. However, the alcoholic extract of R. Canina L. did not change the immobility time in the animals when used intraperitoneally and intracerebroventricularly.Conclusion: It could be concluded that the water extract of R.Canina can inhibit depression induced by FST in mice. Since there are some components in the extract that can interact with D2 dopamine receptors in the brain, it is likely that the extract induced its antidepressant effects via such mechanism.

Introduction: Dexamethasone is a synthetic glucocorticoid with possible effects on anxiety and depression because it has direct effects on the hypothalamus-pituitary-adrenal (HPA) and interacts with several neurotransmitter systems such as GABA and glutamate.Methods: Levels of anxiety and depression in rats were measured 40 minutes and 24 hours, respectively, after subcutaneous injection of Dexamethasone Sodium-Phosphate (DEX) 0.5, 1, 5, 10, 20, 30 mg/kg (saline 1ml/kg) in the elevated plus maze and forced swimming test.Results: The results of anxiety test showed a significant decrease in the percentage of open arm time and open arm entries in DEX (1 mg/kg) group compared to the saline groups. The percentage of time spent in the open arms significantly increased in DEX (20mg/kg) compared to the saline group. In terms of locomotor activity (total number of open and closed arms), significant decrease was observed in DEX (1 mg/kg) compared to the saline group. Also, a significant difference between DEX 1 and 20 mg/kg groups was observed. Comparative assessment of depression during total immobility time showed significant increase in DEX (1 mg/kg) compared to saline and also a significant decrease was observed in DEX (30 mg/kg) compared to the saline groups. A significant difference in latency to immobility was also detected between DEX 1 and 30 mg/kg groups.Conclusion: Our findings suggest that administration of DEX induced dual effects on anxiety and depression; anxiogenic and depressant effects were observed at lower doses, while anxiolytic or antidepressant effects were detected at higher doses.