Physiology and Pharmacology
Year:2002 | Volume:5 | Issue:2|Papers Count:13

In the present study, the effect of GABA (γ-aminobutyric acid) receptor agonists and antagonists on pain induced by sciatic nerve ligation was investigated in mice. Antinociceptive effect of morphine or GABA receptor agonists was examined 14days after unilateral ligation of sciatic nerve by hot-plate test. Intraperitoneal injection of different doses of morphine (3, 6, and 9 mg/Kg), muscimol (0.5, 1, and 2 mg/Kg) or baclofen (I, 2.5, and 5 mg/Kg) induced a dose-dependent antinociception in both intact and nerve-ligated mice. In this respect, the response for morphine but not that of muscimol or baclofen was significantly less in nerve-ligated mice than that induced in intact animals. The responses induced by muscimol or baclofen in nerve-ligated animals were reduced by bicuculline and CGP35348 respectively. However, morphine (3 mg/Kg) in combination with different doses of muscimol or baclofen tends to enhance the antinociceptive effect of morphine in nerve-ligated mice. Subcutaneous injection of the opioid receptor antagonist naloxone (0.5, 1, and 2 mg/Kg; s.c.) reduced the response induced by muscimol or baclofen in nerve-ligated animals. It can be concluded that reducing effect of naloxone on antinociceptive effect of muscimol and baclofen is mediated through GABAA and GABAB receptors respectively and, at least part of the antinociception induced by GABAA receptor may be affected through opioid receptor mechanism.

In this study, the role of adenosine A1 receptors of CA1region of the hippocampus was investigated on amygdala kindled seizures in rats. A 3-polar electrode and two guide cannules were implanted in amygdala and CA1 region of hippocampus respectively. The results showed that in kindled animals, bilateral injection of N6-Cyclohexyladenosine (CHA), an adenosine A1 receptor agonist 5, 15, and 60 min after stimulation at doses of 0.1, 1, and 10 µM into the CA1 region significantly decreased the duration of after-discharge and stage 5 of seizure and increased the latency of stage 4, but there was no changes in seizure stage. Also, bilateral injection of 1, 3-dimethy 1-8-cyclopenthylxanthine (CPT), an adenosine A1 receptor antagonist at doses of 0.5 and 1 µM into the CA1 region did not produce any changes in the seizure parameters. Intrahippocampal pretreatment of CPT (1 µM) before CHA treatment (0.1 and 1µM) significantly reduced the effects of CHA on seizure parameters. Therefore, it may be concluded that CA1 region of the hippocampus plays an important role in spreading of seizure spikes from amygdala to other brain regions and activation of adenosine A1 receptors in this region participates in anticonvulsant effects of adenosine agonists.

Although parenteral administration of deferoxamine is the most effective treatment for acute or chronic toxicity of iron overload states, but due to its poor absorption through gastrointestinal tract, it is not appropriate to use it through oral route. In this study, urinary excretion of iron by oral deferoxamine solution was studied in male adult rats. Oral administration of deferoxamine (500 mg/Kg) in iron-overloaded animals leads to urinary iron excretion by a factor of 33% compared .to parenteral admimnistration of deferoxamine (100 mg/Kg; i.p.). The rate of iron excretion reached to 88% when deferoxamine was injected directly into the duodenum and the gastric acid hydrolysis was avoided.Addition of 0.5% chitosan to oral deferoxamine solution did not produce any significant change in iron excretion. However chitosan at a concentration of 1.5% caused a significant increase in absorption of deferoxamine within duodenum, and iron excretion was about 99% as effective as the amount obtained by the parenteral deferoxamine. Based on these results, gastric acid has a significant degrading effect on deferoxamine. Therefore, it is suggested that coated formulations should be used for oral administration of this effective drug in treatment of iron poisoning.

In this study, the interaction of type I hexokinase (HK I) with mitochondria obtained from biopsies of normal and tumoral tissues of human brain was investigated. This effort was undertaken with the aim of exploring possible differences in the mode of association of the enzyme with the outer mitochondrial membrane in the above-mentioned sources. The results showed that the two sites for binding of HK I based on extensive studies carried out on rat brain mitochondria are similarly present in the human brain mitochondria. This was achieved by preparing mitochondria from specified tissues by differential centrifugation technique. The susceptibility of enzyme towards release by G6P and KSCN and its rebinding was then studied using mitochondria of liver and brain tissues. Monoclonal antibodies provided useful tools to compare topological surface changes on mitochondria from various tissues. Differences in the microenvironments of HK binding as reflected by the presented data are suggested to be of importance in regulation of the catalytic potential of the bound enzyme. The real metabolic significance of this association in relation to cancer and its practical importance need further investigation.

Post-operative pain and its management remains one of the most important issues in the field of surgery and health care system. On the other hand, opioid drug abuse has a large prevalence in Iran. Formalin test has been used as a method for assessing pain and analgesia in rats. In the present study, the post-operative pain in morphine addicted rats was compared with that of non-addicted ones using formalin test. For this purpose, 26 rats were chosen and randomly divided into two groups. First group received morphine sulphate in their drinking water for 21 days. The other group received only tap water. On the day of their assessment, a longitudinal incision (1-cm) was made through skin fascia of their plantar aspect of one foot under ether anesthesia. One hour later, their pain was assessed with formalin test through intra-plantar subcutaneous injection of 0.05 ml of 2.5% formalin solution. Our results showed that acute pain (the first 5 minutes after injection) in both groups was not different significantly, but chronic pain (the next 15-45 minutes) was much intense in morphine-addicted rats.

Dopamine is the predominant catecholamine neurotransmitter in the mammalian brain. The dopamine-induced hyperglycemia has already been reported. We have shown previously that activation of D2 like receptors produced a significant hyperglycemia.In the present study the effect of two selective D2 agonists, bromocriptine and quinpirole on plasma glucose level was compared in male albino mice. Blood samples were obtained from retra-orbital sinus by the Stone procedure and blood glucose was measured by orto-toluidine method. Bromocriptine (0.125, 0.5, and 2 mg/Kg) and quinpirole (0.25, 0.5, and 1 mg/Kg) caused marked hyperglycemia. The effect of bromocriptine and quinpirole was dose- and time-dependent, producing the maximum response 60 and 150 minutes after drawing the first blood samples. Bromocriptine-induced hyperglycemia was elevated by sulpiride 25 mg/Kg. while decreased by sulpiride (100 mg/Kg) and domperidone (30 mg/Kg). The blocking effect of sulpiride was developed from the beginning of experiments, while the effect of bromocriptine was observed one hour after the injection. Quinpirole-induced hyperglycemia was prevented by domperidone but not by sulpiride.It can be concluded that central and peripheral metabolic pathways may be involved in bromocriptine-induced hyperglycemia through D2 receptors, while quinpiroIe-induced hyperglycemia is produced through peripheral mechanisms by other dopamine receptors which are insensitive to sulpiride.

Leukemias are neoplasms that originate from malignant cells related to hematopoietic stem cells. Maturation of malignant cells is prematurely arrested and they merely proliferate. It is generally an accepted concept in oncology that the malignancy must be eliminated. In the recent decade, new therapeutic treatments have been introduced based on chemicals like cytokines and chemotherapeutic agents with less complications. This generally-accepted viewpoint in cancer treatment is called differentiation therapy. The present study is based on this method of treatment using cytokines and cytotoxic drugs.The K562 cells were exposed to different concentrations of γ-interferon, erythropoietin, cytarabin, adriamycin and vincristin. After determination of optimum doses for these drugs, the cells were treated with them for 7 days and then cytospin smears were prepared from the cells and stained with benzidine and Wright methods and their differentiation was evaluated. For quantitative analysis of differentiation, rate of heme production was measured. For statistical analysis χ2 and student’s t-test were used.The results showed that although all of the above-mentioned drugs except vincristin can have differentiative effect compared to control group (P<0.05), but their combination decreases the differentiation.

Cholesterol is an essential constituent of neuronal membrane. It is a lipid-like substance that is present in animal diets, and foodstuffs like butter contains large amounts of cholesterol and saturated fatty acids. Therefore, it is predicted that dietary butter affects structure and function of neurons. In this study the effect of butter (as an animal oil) on spatial learning task was investigated using T-maze in male rats.The animals were divided into 4 groups; the first group as control was fed with rat chow diet and the experimental groups were fed with diets containing 10% butter ad libitum for 2,3,and 4 weeks respectively. Thereafter, for 9 consecutive days rats were trained for spatial learning using T-maze task. The results showed that administration of dietary butter for 2 weeks increase spatial learning (P<0.05) compared to control group. The facilitative effect of dietary butter prior to training may be due to the presence of cholesterol or saturated fatty acids in butter.

In the present study the possible analgesic effect of flower (with 44.6% humidity) and leaf (with 40% humidity) extracts of Tanacetum parthenium was investigated.For this purpose, formalin test (chronic pain model) was used and sodium salisylate (SS; 200 mg/Kg; i.p.) was used as positive control and the effect of extracts at doses of 10, 25, and 50 mg/Kg (i.p.) were evaluated. The results showed that extracts can decrease pain in both phases of formalin test, especially in the first phase and sodium salisylate can decrease pain significantly in second phase of the test (P<0.01). These effects were also observed for minimal doses of the extracts (P<0.01). The minimum lethal dose of the extracts is estimated about 4000 mg/Kg for the flower extract and 3000 mg/Kg for the leaf extract.It has been reported that these extracts like SS have an inhibitory effect on prostaglandin synthesis. Because the extracts have analgesic properties in both phases of formalin test compared to SS which was only effective in the second phase, it may be suggested that the extracts are engaged in both central and peripheral analgesic mechanisms.

The aim of this study was to determine the effect of nifedipine cream on wound healing in diabetic rats. For this purpose, 36 male Wistar rats (180-200 g) were randomly divided into four groups. At first, two groups of rats were made diabetic using streptozotocin (70-80 mg/Kg; i.p.) and the other two groups were considered as control. After observing symptoms of diabetes including increased blood sugar (250-300 mg/dl), a wound with a diameter of 1.5 cm was made on the dorsum skin of each rat under sterile conditions. Nifedipine cream (3%) was then applied to one group of diabetic rats and one group of normal rats. The other two groups were treated with placebo. Thereafter, biopsies were taken from the healing regions at the third, seventh, and the wound closure days. The microscopic findings showed that there was a significant difference between the group receiving nifedipine and the group treated with placebo regarding both inflammation and growth phases (P<0.0005). In addition, there was a significant difference between the diabetic groups for both phases (P<0.001), while there was only a significant difference between the two control groups for the inflammation phase (P=0.05). Therefore, it can be concluded that nifedipine cream is effective in wound healing.

Increased activity of mesolimbic dopaminergic pathway within ventral tegmental area (VTA) by morphine results in psychologic dependence. It is argued that function of dopamine receptors could be affected by ascorbic acid (AA). Furthermore, AA can decrease the withdrawal syndrome signs in addicted animals and may postpone the development of morphine dependence. In the present study, the possible role of AA on acquisition and expression of morphine-induced conditioned place preference (CPP) was investigated in mice.In this study, female Swiss-Webster mice (20-25 g) were used and a biased method was performed for induction of CPP. The results showed that subcutaneous injection of morphine (1-10 mg/Kg) induced CPP in a dose-dependent manner. In addition, intraperitoneal administration of AA (1-1000 mg/Kg) failed to induce any aversion or preference effects. Meanwhile, administration of AA (I -1000 mg/Kg) on the test day reduced the morphine effect, but not in a dose-dependent manner. The chronic administration of AA (1-1000 mg/Kg; i.p.) reduced the morphine effect as well. Therefore, it can be concluded that motivational effects of morphine can be affected dramatically by AA, but the drug may not act via a single mechanism.