Physiology and Pharmacology
Volume:17 Issue: 3, 2014

During the recent decades, substantial changes are made in the borders and contents of physiology as a basic course for the students in medicine. Here some strategies are presented to preserve the classical and integrative approaches in teaching physiology, while these approaches extent our knowledge to molecular, sub-cellular and cellular levels.

Orexins are novel neuropeptides that are localized in neurons in the lateral hypothalamus. They are implicated in a wide variety of physiological functions. Orexin peptides and receptors are found in many peripheral organs such as kidneys. It has been demonstrated that exogenous orexin-A can induce protective effects against ischemia–reperfusion injury in many organs. The goal of this study was to determine the effect of orexin-A on the hepatic dysfunction and histological damage induced by renal ischemia/ reperfusion at an early stage. Pentobarbital anaesthetized rats were prepared for measuring renal functional variables. Ischemia was induced by bilateral renal artery clamping for 30 min followed by a 1 h reperfusion period. In orexin-treated rats, it was infused at 500 pmol·kg−1·min−1 (i.v.) from the beginning of pre-ischemic (pretreatment) clearance period. The liver was examined using light microscopy. The renal ischemic challenge resulted in hepatic functional and histological damages, which were associated with decreased creatinine clearance during the reperfusion period. In orexin-treated rats, the functional and histological damages to the liver were improved along with the decrease in creatinine clearance being smaller than those of the non-treated rats. Orexin-A exhibited an ameliorative effect against renal ischemia/reperfusion-induced lesions in the liver.

Transplantation of embryonic ventral mesencephalic (VM) dopamine neurons into the striatum is a currently explored therapeutic strategy for treatment of patients with patients with Parkinson''s disease (PD). However, this strategy has been limited with poor cell survival, generally ranging from 5-20%. In this study, we investigated the effect of potassium channel blocker of tetraethylammonium (TEA) and B vitamins supplementation on the efficacy of cell replacement therapy in the treatment of 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. Cell suspension was prepared from embryonic day 14 (E14) VM of rat fetuses and was transplanted into striatum of Parkinsonian rats after overnight hibernation with TEA or B vitamins. The Parkinsonian rats were also treated with TEA or B vitamins for two weeks after transplantation. Severity of Parkinsonism was assessed by apomorphine-induced rotational test in several steps before and after transplantation. 1- Transplantation of VM cell suspension significantly decreased behavioral symptoms of Parkinsonism in the apomorphine-induced rotational test. 2-TEA treatment further decreased these symptoms. 3- B vitamins treatment had no additional effect in amelioration of the symptoms. 4-Treatment with both TEA and B vitamins also further decreased behavioral symptoms, which in one post-transplantation test was even more than the effect of TEA alone. TEA, especially in combination with B vitamins supplementation, can increase the efficacy of cell replacement therapy in the 6-OHDA rat PD model.

Arginine-phenylalanine-amide-related peptide-3 (RFRP-3) and kisspeptin are believed to be inhibitor and stimulator of gonadotropin releasing hormone (GnRH) secretion, respectively. The aim of the present study was to compare the effect of lactation on the expression of RFRP-3 mRNA in dorsomedial hypothalamic nucleus (DMH) and KiSS-1 mRNA in arcuate nucleus (ARC) of hypothalamus in lactating and non-lactating rats. Fourteen rats of the Sprague-Dawley strain were randomly allocated into three groups. The non-lactating rats (n=5) were separated from their pups immediately upon parturition. The lactating rats were allowed to suckle five pups for eight days (the period of increasing of lactation). Relative expressions of RFRP-3 and KiSS-1 mRNAs compared to the control group were determined in DMH and ARC of hypothalamus, respectively, by using real-time PCR. Mean of relative expression of RFRP-3 mRNA in DMH in the lactating group was higher than that of the non-lactating rats (P=0.001). Relative expression of KiSS-1 mRNA in ARC did not show any difference between the lactating and the non-lactating rats (P=0.4). Increase of RFRP-3 mRNA expression in DMH of hypothalamus during the increase of milk production in rat may be the inhibitory factor for GnRH secretion. Whereas, no change in KiSS-1 mRNA expression in the ARC of the same rats may indicate the lower activity of this nucleus in the expression of the gene in both groups postpartum.

Beta-actin is a housekeeping gene, which is used as an internal standard in various biological studies. Recently, it was reported that the expression of commonly used housekeeping genes including ß–actin changes in disease states or under certain experimental conditions. Based on the reports about the effects of sex hormones on the expression of the ß- actin gene, in this study, we examined the sex differences in the expression levels of ß- actin gene in different tissues of the rat.

Total RNA was extracted from the brain, spinal cord, heart, kidney and liver tissues in male and female rats as well as uterus in females. The RT-PCR method was used to measure the levels of ß-actin gene expression in all tissues.

The expression of ß-actin gene in the brain and spinal cord of male rats was significantly higher than its expression in female animals (P<0.05). It was also found that the expression of ß-actin gene in the heart and uterus of females were significantly higher in comparison with other tissues (P<0.001 and P<0.05 respectively). Similarly, ßactin gene expression in the heart tissue of male rats was significantly higher than other tissues (P<0.001).

It is suggested to validate the constancy of ß-actin gene expression under the experimental condition, before using this house keeping gene as an internal standard in molecular biology studies.

The prostaglandin E2 (PGE2), a cyclooxygenase (COX) product, play critical roles in the synaptic plasticity. Therefore, long term use of COX inhibitors may impair the synaptic plasticity. Considering the wide clinical administration of aspirin and its unknown effects on information processing in the brain, the effect of aspirin and sodium salicylate on the short term synaptic plasticity was investigated.

Field excitatory post synaptic potential (fEPSP) from stratum radiatum of CA1 neurons were recorded following Schaffer collateral stimulation in rats receiving aspirin in drinking water (2 mg/ml) for 6 weeks or sodium salicylate (six injection of 300 mg/kg, IP, twice daily) for 3 days. In order to examine the short-term synaptic plasticity, paired pulse stimulations with inter pulse intervals (IPI) of 20, 80, and 200 ms were applied and paired pulse index (PPI) was calculated.

The data showed that both sodium salicylate and aspirin decreased basal synaptic responses, although this change was significant in the sodium salicylate group, but not in aspirin treated rats (ANOVA; P<0.001). Sodium salicylate significantly increased PPI at 20 ms IPI (%90.7±1.6, n=5Vs. control: %76.1±1.5, n=5). Also significant increase in PPI was observed in aspirin treated rats (%125.9±6.6, n=5) at 20 ms IPI compared to control ones (%76.3±2.4, n=5, P<0.05, unpaired t-test).

In summary, our study suggests that aspirin and sodium salicylate may affect synaptic transmission and short term synaptic plasticity in the rat hippocampus.

There are about 120 million people around the world who suffer from allergies. This is a huge number and all these individuals currently use anti-allergic drugs that are associated with numerous side effects. In order to find an appropriate complementary drug from traditional folk medicine, Teucrium polium was examined. Prednisolone was used as a control anti-allergic drug.

Male Wistar rats were used and randomly divided into different experimental groups. Ovalbumin was used to induce allergy and sensitization challenge was confirmed by the presence of sneezing and changes in the level of eosinophils and IgE. Eight days after allergy induction, Teucrium polium (4, 8 and 12 mg/kg) was administrated orally for eight days. Blood samples were collected on day 16 and blood cell count and IgE concentration were determined. Positive control animals were given 2 mg/kg prednisolone in a similar manner.

The data showed that ovalbumin could induce sensitivity and increased eosinophils and IgE levels. Oral treatment with Teucrium polium showed significant decrease in the number of eosinophils (p<0.01) and serum levels of IgE (p<0.01). The effects of this plant extract were comparable to those observed in prednisolone-treated group. In addition, Teucrium polium effects remained 8 additional days after the termination of drug treatment.

These results suggest that oral Teucrium polium treatment could be a promising treatment for allergic conditions. Therefore, our study contributes to expand the knowledge on diverse pharmacological effects of Teucrium polium extract.

Cognitive dysfunction is recognized as a significant feature of multiple sclerosis (MS). Oxidative stress plays an important role in the pathogenesis of MS. Toxic demyelination by ethidium bromide (EB) is one of the common methods for induction of MS, which leads to neuronal death by production of free radicals and enhancement of oxidative stress burden. According to previous pharmacological studies, saffron extract acts as a free radical scavenger. Accordingly, in the present study the effect of short-term microinjection of saffron extract on the process of spatial memory and lipid peroxidation in the hippocampus was assessed in an experimental model of MS.

One week after MS induction by EB (0.01 %), animals of the experimental group were treated by saffron extract (5 and 10 μg/rat) for 3 consecutive days. Following the treatment period, Morris Water Maze test was carried out and hippocampi of both sides were dissected and used for measurement of a lipid peroxidation marker (MDA) in the end.

Based on the results of the present study, short-term treatment by saffron extract significantly ameliorated spatial memory in experimental models of MS (P<0.05). MDA in the saffron treated group showed a significant reduction compared to the control MS animals (P<0.01).

It seems that treatment with saffron extract is able to prevent memory and learning reduction, through inhibition of lipid peroxidation in an experimental model of MS. However, evaluation of beneficial effects of saffron on the spatial memory and its role in preventing or treating cognitive deficits in MS patients, requires much more extensive molecular studies.

Huntington''s disease is a neurodegenerative disorder in which an increase in the global oxidative stress and a decrease in the antioxidant defense system are observed. Olea europaea''s main phenolic components include oleuropein, dimethyl oleuropein, ligstroside and phenolic oleosides, which can be more than 140 mg per gram of fresh olives and 60-90 mg per gram of dried olive leaves. These phenolic components have great antioxidant and neuroprotective properties. We aimed to study the neuroprotective effects of pretreatment with olive leaf extract on the behavioral signs and antioxidant enzymatic activity in the brains of Huntington animal models.

Rats were divided into 4 groups in separate cages. The first and the second groups received distilled water orally. The third and the fourth groups were gavaged by75 and 150 mg/Kg/day of olive leaf extract, respectively. To induce Huntington’s disease, the animals were intraperitoneally injected with3-NP for 6 days.

Pretreatment with olive leaf extract exerts neuroprotective effects and significantly reduces neurological disorders and increases superoxide dismutase, glutathione reductase and catalase activities.

Although more studies are required to explain the healing mechanism of olive leaf extract, it seems to exert its effects via protecting neurons through its antioxidant properties and its ability to increase enzyme activities including superoxide dismutase, glutathione reductase, catalase.

The concentration and action of ascorbic acid in the central nervous system as a vitamin and also a neuromodulator have exercise-induced fluctuations. The present study was conducted to evaluate the effects of anaerobic exercise alone and associated with the consumption of ascorbic acid as a non pharmacological treatment for reducing seizures and increasing seizure thresholds. In this experimental study, 28 adult male Wistar rats (200-250gr) were divided into four groups including control (PTZ), anaerobic exercise, ascorbic acid and anaerobic exercise plus ascorbic acid. After performing exercise according to the designed protocol, PTZ was used for inducing seizures (80mg/kg, IP) and seizure latency of different stages was analyzed for each group. In anaerobic exercise plus ascorbic acid group, the latency of the onset of seizure in all stages showed a significant increase in comparison with the control (p<0.001). The data showed that stages 2, 3,4 and 5 latency significantly increased in anaerobic exercise plus ascorbic acid group in comparison with the animals treated with ascorbic acid (p<0.05). Seizure related mortality was significantly decreased in ascorbic acid and also anaerobic exercise plus ascorbic acid groups (0%) compared to the control group (57%, p<0.05). In conclusion, these data suggest that the exercise as well as ascorbic acid and also combination of them have a preventive role in PTZ-induced seizure.

Glycyrrhiza glabra (Licorice) has been traditionally used as a medicinal plant in Iran for treatment of diseases such as gastric ulcer and arthrosclerosis. In this study, in order to determine some of its mechanisms, effects of hydroalcoholic extract of Glycyrrhiza glabra was examined on the blood pressure in rats. Adult male rats were anesthetized via injection of pentobarbital sodium, then the femoral vein and the femoral artery were canulated for injections and blood pressure recordings, respectively. Blood pressure and heart rate were recorded by pressure transducer linked to A-D instrument power lab. Tested groups were as follows: The first group, received Glycyrrhiza glabra extract (90mg/kg) and equivalent volume of the Licorice solvent (ethanol %70). The second group received Glycyrrhiza glabra extract and acetylcholine (0.01 mg/kg). The third group received Glycyrrhiza glabra extract and epinephrine (0.04 mg/kg). The data showed a significant decrease of blood pressure (mean blood pressure, systolic and diastolic pressure) in the presence of licorice extract, licorice and epinephrine, licorice and acetylcholine compared to the control condition. It can be concluded that Glycyrrhiza glabra has a hypotensive effect on blood pressure via modulation of adrenergic system and synergistic effect with cholinergic system.