ABSTRACT
Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. Previous studies have referred to the effects of morphine on smooth and pulmonary muscles, but the effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats
Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control [the mice were kept in their cages and received food and water], morphine receiving group, fatigue group [the mice in this group were kept running on a treadmill. for120 minutes at a rate of 20 meters per minute], and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase [LDH] and creatine phosphokinase [CPK]
Results: Administration of morphine to the fatigue group decreased running time compared with the control group [P=0.009]. Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH [P=0.009] and CPK [P=0.008]
Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers [LDH, CPK]
ABSTRACT
Background: IL-17/IL-23 axis plays an important role in the pathogenesis of severalautoimmune diseases such as experimental autoimmune encephalomyelitis [EAE] andmultiple sclerosis [MS]. The immunomodulatory properties of ginger are reported in previous studies
Objective: To evaluate the effects of ginger extract on the expressionof IL-17 and IL-23 in a model of EAE
Methods: EAE was induced in C57BL/6 miceby immunization with myelin oligodendroglial glycoprotein and then treated with PBSor ginger extracts, from day +3 to +30. At day 31, mice were scarificed and theexpression of IL-17 and IL-23 mRNA in spinal cord were determined by using realtime-PCR. The serum levels of cytokines were measured by ELISA
Results: ThemRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL-17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group[p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively]. In 200 mg/kg gingertreatedEAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL-23 levels were significantly decreased as compared to PBS-treated EAE mice [p<0.05,p<0.001, p<0.001 and p<0.05, respectively]. Moreover, 300 mg/kg ginger-treated EAEgroup had significantly lower expression of IL-17, P19 and P40 in CNS and lowerserum IL-17 and IL-23 levels than PBS-treated EAE group [p<0.02, p<0.001, p<0.001,p<0.03 and p<0.004, respectively]
Conclusion: Ginger extract reduces the expressionof IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment ofMS could be considered in further studies
ABSTRACT
Background and Aim: Oxidative stresses are involved in neuronal degeneration of substantia nigra and thereby induction of Parkinson's disease. It is reported that Foeniculum Vulgare L. can affect lactating and modulating dopaminergic system activity and antioxidant activity as well. In the present study, the effects of methanolic extract of Foeniculum Vulgare seeds on a Parkinson's disease model induced by ICV injection of 6-hydroxydopamin [6-OHDA] in female rats were investigated
Materials and Methods: In this experimental study, 60 female rats were randomly divided into 6 equal groups including saline, Parkinson's disease and Parkinson's groups which were treated by different doses of the extract. Parkinson's disease was induced by i.c.v injection of 6-OHDA. Methanolic extract of Foeniculum Vulgare seeds [100 and 200 mg/kg] was gavaged through two ways including repeated gavage [14 days before and 14 days after 6-OHDA injection] and acute gavage [once every day for 14 days after 6-OHDA injection]. The induced Parkinson`s disease was evaluated using Rotarod and Wire grasping tests on the day 14[th] after 6-OHDA injection
Results: The findings of the study demonstrated that repeated gavage of Foeniculum Vulgare extract improved motility and muscle tone in Parkinson's animals [p<0.05]. However, acute gavage of the extract had no significant effect on the performance of Parkinson's animals
Conclusion: Results of the current study showed that chronic administration of Feoniculum Vulgare extract may improve Parkinson's symptoms in female rats
ABSTRACT
Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline
Methods: 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus [VAC] ethanolic extract orally. The last groups were treated with 40 micro g/kg of estradiol valerat. Step-through passive avoidance [STPA] test was used for the evaluation of learning and memory. The hippocampal estrogen receptor alpha [ERalpha] expression was measured using Real-Time PCR
Results: The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group [all P<0.05]. Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ER alpha and prevented the decrease in uterine weight of ovariectomized rats
Discussion: Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ER alpha gene expression in the hippocampal formation
ABSTRACT
Background: Chronic use of opioids usually results in physical dependence. The underlying mechanisms for this dependence are still being evaluated. Transient receptor potential vanilloid type 1 [TRPV1] are important receptors of pain perception. Their role during opioid dependence has not been studied well. The aim of this study was to evaluate the effect of morphine-dependence on the expression of TRPV1 receptors in the amygdala and CA1 region of the hippocampus
Methods: This study used four groups of rats. Two groups of rats [morphine and morphine+naloxone] received morphine based on the following protocol: 10 mg/kg [twice daily, 3 days] followed by 20, 30, 40 and 50 mg/kg [twice daily], respectively, for 4 consecutive days. Another group received vehicle [1 ml/ kg] instead of morphine given using the same schedule. The morphine+naloxone group of rats additionally received naloxone [5 mg/kg] at the end of the protocol. The control group rats received no injections or intervention. The amygdala and CA1 regions of the morphine, saline-treated and intact animals were isolated and prepared for real-time PCR analysis
Results: Administration of naloxone induced withdrawal signs in morphine-treated animals. The results showed a significant decrease in TRPV1 gene expression in the amygdala [P<0.05] but not the CA1 region of morphine dependent rats
Conclusion: TRPV1 receptors may be involved in morphineinduced dependence
ABSTRACT
Toxoplasma gondii is a worldwide prevalent zoonotic parasite which causes toxoplasmosis. An appropriate vaccine for animals could interrupt the circle between animals and humans. Our previous study showed that excreted/secreted antigens [E/ SA], derived from the peritoneum of mice infected with T. gondii tachyzoites could be considered as a good candidate for animal vaccination. Interleukin-10 [IL-10] inhibits proliferation of B and T lymphocytes and induces homeostasis in immune system responses. However, since IL-10 has also been shown to suppress the killing of T. gondii by human macrophages, the aim of this study was to evaluate IL-10 serum levels after vaccination with T. gondii E/SA prepared in vivo. T. gondii tachyzoites were inoculated in the peritoneum of mice and harvested E/SA were used as a vaccine, with and without adjuvant, in T. gondii infected and un-infected mice. IL-10 serum levels were evaluated using the ELISA technique. The data showed that although serum levels of IL-10 were not changed at the early phases, they were elevated at the end phases of vaccination with T. gondii E/SA. Based on these and our previous results, it can be concluded that in vivo prepared T. gondii E/SA could be considered as a good candidate for animal vaccination
Subject(s)
Animals, Laboratory , Antigens, Protozoan , Vaccination , Interleukin-10/blood , MiceABSTRACT
Background and purpose: Morphine addiction and morphine withdrawal syndrome are of main problems in human societies. In the present study, effect of nicotine on the strength of physical and psychological dependency, produced by single and repeated doses of morphine, was investigated
Material and method: Male wistar rats were dependent to morphine with single and repeated dose protocols. In the single dose protocol, rats received only one dose of morphine and 24h later were given Naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24h after the last dose [8th day] were given Naloxone. In the single dose protocol, rats were given one dose of nicotine 30 min before Naloxone. However in the repeated doses they received nicotine 15 min before morphine for 4 days from 4th day to 7th day. 5 min after Naloxone each rat?s behavior was captured for 30 min. then physical and psychological signs of withdrawal syndrome were recorded
Results: Results showed that injection of repeated and even single dose of morphine can produce dependency. Nicotine consumption attenuated strength of withdrawal syndrome signs, specially increasing weight excrement and total withdrawal score in single dose protocol and weight excrement increasing, weight decreasing, place aversion, and total withdrawal score in repeated dose treatment
Conclusion: Based on our data, even a single dose of morphine can produce dependency in rats. Conversely, Nicotine consumption attenuates strength of withdrawal syndrome signs
ABSTRACT
Morphine addiction and morphine withdrawal syndrome are the two main problems of today's human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose [the 8th day] were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat's behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine
ABSTRACT
Occult hepatitis B infection [OBI] is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-gamma and +1188 of IL-12 with their serum level in patients suffering from OBI. In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen [HBsAg] and anti-HBc by ELISA. The HBsAg[-]/anti-HBc[+] samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-gamma. In addition, the serum levels of IL-12 and IFN-gamma were also determined by ELISA. Results of this study demonstrated that, 352 [9.5%] out of 3700 blood samples were HBsAg[-]/anti-HBc[+]and HBV-DNA was detected in 57/352 [16.1%] of HBsAg[-]/anti-HBc[+] samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-gamma were also not associated with serum level of cytokines. According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-gamma would not affect the expression of both cytokines at serum level in OBI patients
Subject(s)
Humans , Male , Female , Interferon-gamma/genetics , Interleukin-12/genetics , Occult Blood , Polymorphism, Genetic , Gene Expression , Hepatitis B Antigens/blood , Cytokines/blood , Socioeconomic FactorsABSTRACT
Opioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes. Addiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery [MCA]. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke. Morphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals [P< 0.05] at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke [P< 0.05]. Our data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke
Subject(s)
Male , Animals, Laboratory , Morphine/adverse effects , Brain Ischemia , Rats, Wistar , Stroke , Morphine Dependence , Brain Edema , Body Weight ChangesABSTRACT
The present study was performed to determine the effect of intracerebroventricular [ICV] administration of W- 7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. This study was carried out on male wistar rats, weighing 200-250 g. Morphine was administered daily [15 mg/kg for 8 days]. The threshold to thermal nociceptive stimuli was measured by tail-flick test. W-7 [0.25, 0.5 and 1 micro mol/rat] was injected through ICV. Maximal possible effect percentage [MPE%] was considered as analgesia index. Our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of W-7 [0.5 and 1 micro mol/rat] decreased the development of tolerance to it. In conclusion these data showed that chronic injection of W-7 inhibited the development of morphine tolerance which indicates that calmodulin and its dependent pathways may play a role in the morphine tolerance processes
Subject(s)
Animals , Analgesics, Opioid/pharmacology , Calmodulin/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Morphine/pharmacology , Sulfonamides/pharmacology , Injections, IntraventricularABSTRACT
High levels of regulated oncogen-alpha [GRO-a] expression have been observed in the liver. GRO-a stimulates proliferation of epithelial cells and induction of rolling and extravascular migration of neutrophils and mononuclear cells. Given the above observations, this chemokine was chosen to be analyzed in freshly isolated and cultured hepatocytes. In this study, hepatocytes [2_106 cell/ml] were isolated from male Sprague Dawley rat liver and cultured on plates that were pre-coated with collagen type-I matrix. The western and northern blot analyses were employed to detect GRO-a at the protein and mRNA levels in freshly isolated and cultured hepatocytes in response to isolation and heat shock stresses. GRO-a was shown to be expressed by isolated rat hepatocytes immediately after isolation and early culture and decreased with time. mRNA was also expressed in freshly isolated cells [0 h] and did not decrease after 48h of culture and further time points [P<0.01]. These results also demonstrated that expression of GRO-a by hepatocytes increased in response to heat shock at different time points in comparison with the control [P<0.01]. These results demonstrated that the isolation and heat shock stresses induced the expression of GRO-a in hepatocytes in a time-dependent manner. Thus, it seems that hepatocytes mimic the experiences that the liver encounters after injury in vivo. In such a situation, liver produces stress related agents like chemokines to overcome injurious conditions
Subject(s)
Male , Animals, Laboratory , Hepatocytes , Heat-Shock Proteins , Gene Expression , Rats, Sprague-Dawley , RNA, Messenger , Blotting, Northern , Blotting, Western , DNA , LiverABSTRACT
Although, type 2 diabetes is the most frequent type of diabetes, its main cause is yet to be clarified. Several environmental and genetic parameters are believed to be involved in diabetes. It has also been established that cytokines play key roles in pathogenesis of diabetes. Expression of cytokines is different from person to person and in different societies. Several studies showed that polymorphisms of +874 of interferon-gamma [IFN-gamma] and -590 of interleukin-4 [IL-4] are associated with the regulation of expression of these genes. This study was aimed to find polymorphisms of these regions in type 2 diabetes patients. In this experimental study peripheral blood samples were collected from 160 type 2 diabetic patients and 160 healthy controls. DNA was extracted by salting out method. Polymorphisms of +874 of 1FN-gamma and -590 of IL-4 were analyzed by ARMS-PCR and RFLP-PCR. Our findings indicated that TT genotype of IFN-gamma was increased in type 2 diabetic patients compared to the control but difference was not significant. Our results didn't show any significant difference between IL-4 genotype in diabetic and healthy controls either. Our results suggested that TT genotype of IFN-gamma can be associated with diabetes. This association can be described by the fact that over expression of IFN-gamma shifts immune system to Th 1; therefore, pancreatic cells can be miscarried by immune cells
Subject(s)
Humans , Male , Female , Interferon-gamma , Polymorphism, Genetic , Diabetes Mellitus, Type 2 , Genotype , Case-Control Studies , Polymerase Chain ReactionABSTRACT
Occult hepatitis B infection [OBI] is defined as a form of hepatitis B that despite absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. Genetic and immunological differences appear to play important roles in producing OBI. Therefore, this project was aimed to examine the expression of a chemokine receptor [CCR5] on CD8[+] T cells of OBI patients. In this experimental study, 3,700 HBsAg- plasma samples were collected. Samples were tested for anti-HBc antibody and all of HBsAg-/anti-HBc[+] samples were screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases. Also, flow cytometry analysis was performed to examine the expression of CCR5 on CD8[+] T cells of OBI patients. Results of current study showed that 352 [9.5%] cases of samples were positive for anti-HBc. Examination of HBsAg/anti-HBc[+] samples for HBV-DNA by PCR showed that 57 [16.1%] cases had HBV-DNA. Flow cytometric studies indicated lymphocytosis in these patients; however, the number of cells which expressed CD8[+] and CCR5 is decreased significantly in patients, compared to healthy control. In addition to CD8[+] T cells, the expression of CCR5 is also decreased on all immune cells. One of the chemokine receptors which are expressed by CD8[+] T cells is CCR5 and these cells are recruited to infected tissues, including liver by CCR5. Therefore, based on results of this investigation, one may conclude that due to the decreased expression of CCR5, the CD8[+] T cells are unable to respond to the chemokines [CCR5 ligands] and, hence, can not immigrate to the infected liver and incorporate in clearance of hepatitis B virus
Subject(s)
Humans , Receptors, CCR5/analysis , CD8-Positive T-Lymphocytes , Hepatitis B Surface Antigens , Hepatitis B Core Antigens , Hepatitis B virus , DNA, Viral , Polymerase Chain Reaction , Flow CytometryABSTRACT
In the present study, we compared the intensity of physical dependency, mortality rate and weight changes in some common methods for inducing morphine dependency. Six common different methods for morphine dependency were chosen in wistar rats. In all methods, morphine dependency was induced by repeated morphine injection. Precipitation of morphine withdrawal signs were performed on the last day in each method, 4 hours after the last morphine injection for 20 minutes. The withdrawal signs included: vertical jumping, wet dog shakes, diarrhea, teeth chattering, ptosis, head shakes and rearing. Our results demonstrated that all groups of treated rats showed withdrawal signs following naloxone challenge. However, the intensities of withdrawal signs [vertical jumping, wet dog shakes, diarrhea, teeth chattering, head shakes and rearing] were significantly different among these methods. Also, mortality rate and amount of weight loss were significantly different among the different methods. This study demonstrates that different experimental methods of morphine dependency can induce different intensities of withdrawal signs, mortality rate and weight loss
Subject(s)
Animals, Laboratory , Naloxone , Rats, Wistar , Weight LossABSTRACT
The aim of present study was to investigate the effect of W-7, a calmodulin antagonist, on a carrageenan-induced rat's paw edema. W-7[50 micro Mol/kg] was given intraperitoneally synchronous with the intraplantar injection of 0.1 ml of 0.5% carrageenan solution. After for hours, paw edema was assessed by calculating the paw volume changes which measured by hydroplethysmometer. In adrenalectomized rats, both adrenal glands were removed. Treatment of animals with W-7 reduced carrageenan-induced paw edema by 50%. In adrenalectomized rats, W-7 was also effective in reduction of paw edema [52%]. There was no significant difference between the effect of W-7 in adrenalectomized and control animals. Our findings suggest that W-7 as calmodulin inhibitor reduce carrageenan-induced paw edema and the inhibitory effect W-7 on edema formation appears not to be dependent on adrenal function