فهرست مطالب

Basic Medical Sciences - Volume:21 Issue: 4, 2018
  • Volume:21 Issue: 4, 2018
  • تاریخ انتشار: 1397/01/05
  • تعداد عناوین: 15
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  • Fatemeh Forouzanfar, Hossein Hosseinzadeh* Pages 347-358
    Chronic neuropathic pain is a common significant and debilitating problem that presents a major challenge to health-care. Despite the large number of available drugs, there are no curative conventional treatments for neuropathic pain. Nowadays, more attention has been focused on the herbal formulation in the field of drug discovery. Therefore, we performed an extensive review about herbal drugs and plants that exhibited protective effects on neuropathic pain. In this review, the beneficial effects of each plant in different neuropathic pain model, either in animals or in patients are reported. Moreover, the possible involved mechanisms for the protective effects are discussed. The more common plants which are used for the treatment of neuropathic pain are included as: Acorus calamus, Artemisia dracunculus, Butea monosperma, Citrullus colocynthis, Curcuma longa, Crocus sativus, Elaeagnus angustifolia, Ginkgo biloba, Mitragyna speciosa, Momordica charantia, Nigella sativa, Ocimum sanctum, Phyllanthus amarus, Pterodon pubescens Benth, Rubia cordifolia and Salvia officinalis. Furthermore, the most pathways which are known to be involved in pain relief by means of herbal remedies are anti-oxidant activity, anti-inflammatory, anti-apoptotic, neuroprotective and calcium inhibitory actions.
    In conclusion, this review suggests that some herbal plants can be suitable candidates for the treatment of neuropathic pain.
    Keywords: Analgesic, Antinociceptive, Chronic pain, Herbal medicine Neuropathic pain
  • Elham Karimi Sales, Sajad Jeddi, Abbas Ebrahimi-Kalan, Mohammad Reza Alipour * Pages 359-363
    Objective(s)
    Trans-chalcone as the parent member of the chalcone series reduces circulating levels of insulin and glucose. However, the cellular mechanism of these effects is poorly understood. Sirtuin 1 (SIRT1) as a direct target of miR-34a controls homeostasis of glucose, and also improves insulin sensitivity. Therefore, the present study for the first time investigated the influence of trans-chalcone on the miR-34a/SIRT1 pathway as a possible mechanism for its hypoglycemic and hypoinsulinemic effects.
    Materials And Methods
    In this study, thirty male rats were randomly divided into three groups (n=10): solvent control (NS), oral administration of trans-chalcone for 2 (N2T) and 6 weeks (N6T) groups. Then, hepatic levels of miR-34a and SIRT1 were measured through the qRT-PCR method.
    Results
    Trans-chalcone reduced food intake, body weight gain, and serum glucose as well as insulin levels. Also, this chalcone inhibited hepatic miR-34a expression and significantly elevated SIRT1 mRNA level.
    Conclusion
    Trans-chalcone as an insulin-sensitizing chalcone partly acts through the miR-34a/SIRT1 pathway.
    Keywords: Liver, MiR-34a, Rat, SIRT1, Trans-chalcone
  • Bing Hu, Xiaoqian Feng, Li Wang, Yinli Song, Xiuqin Ni * Pages 364-369
    Objective(s)
    P2X4R is expressed in immunocyte and lung tissues. It has been a focus in inflammatory responses recently. This study investigated whether blockage of P2X4R attenuates allergic inflammation by modulating T cell response in ovalbumin-sensitized mice.
    Materials And Methods
    Ovalbumin was used to sensitize and challenge for a mouse model. Intranasal application of 5-BDBD, P2X4R antagonist, were performed 3 hr before each airway allergen challenge. The lung was evaluated for P2X4R by real-time PCR and immunofluorescence. Th1/Th2 cytokines in bronchoalveolar lavage fluid were measured by ELISA. T-bet, Gata-3, and p-p38 MAPK were measured by Western blot or real-time PCR.
    Results
    P2X4R was overexpressed in the lung after allergen challenge compared with the control group. Blockage of P2X4R decreased inflammation in the lung, IL-4 expression was reduced as well as IL-5; IFN-γ expression was elevated in BALF in ovalbumin-sensitized mice. Moreover, blockage of P2X4R inhibited ovalbumin-induced increased Gata-3 level and decreased T-bet level.
    Conclusion
    These findings suggest that 5-BDBD ameliorates an ovalbumin-induced asthmatic attack by the downregulation of cytokines related to the Th2 cell.
    Keywords: 5-BDBD, Asthma, Gata-3, T-bet, Th2 cells
  • Mina Mokhtari Hashtjini, Gila Pirzad Jahromi *, Seyed Shahabeddin Sadr, Gholam Hossein Meftahi, Boshra Hatef, Danial Javidnazar Pages 370-375
    Objective(s)
    Post-traumatic stress disorder (PTSD), one of the most devastating kinds of anxiety disorders, is the consequence of a traumatic event followed by intense fear. In rats with contextual fear conditioning (CFC), a model of PTSD caused by CFC (electrical foot shock chamber), deep brain stimulation (DBS) alleviates CFC abnormalities.
    Materials And Methods
    Forty Male Wistar rats (220–250 g) were divided into 5 groups (n=8) and underwent stereotactic surgery to implant electrodes in the right basolateral nucleus of the amygdala (BLn). After 7 days, some animals received a foot shock, followed by another 7-day treatment schedule (DBS treatment). Next, freezing behavior was measured as a predicted response in the absence of the foot shock (re-exposure time). Blood serum corticosterone levels and amygdala c-Fos protein expression were assessed using Enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Furthermore, freezing behaviors by re-exposure time test and general anxiety by elevated plus-maze (EPM) were evaluated.
    Results
    PTSD decreased serum corticosterone levels and increased both amygdala c-Fos expression and freezing behaviors. Therefore, DBS treatment significantly (P
    Conclusion
    We argue that these outcomes might demonstrate the mechanism of DBS treatment, a complete therapeutic strategy, in PTSD patients.
    Keywords: Amygdala, Anxiety behavior, Corticosterone, c-Fos, Deep brain stimulation, Freezing behavior, Post-traumatic stress disorder
  • Tahereh Nikyar, Mahmoud Hosseini, Saeed Niazmand, Mohammad Naser Shafei * Pages 376-381
    Objective(s)
    Cholinergic neurons are important neurons in the Pedunculopontine tegmental nucleus (PPT). In this study, nicotinic receptor of the PPT in central cardiovascular regulation in the anesthetized rat was evaluated.
    Materials And Methods
    Saline, acetylcholine (Ach; doses: 90 and 150 nmol), hexamethonium (Hexa; doses: 100 and 300 nmol) and higher doses of Hexa (300 nmol) Ach (150 nmol) microinjected into the PPT. The femoral artery was cannulated and cardiovascular responses were continuously recorded by a power lab system. After injection of drugs, peak changes of mean arterial pressure (∆MAP), systolic blood pressure (∆SBP) and heart rate (∆HR) calculated and compared with saline group.
    Results
    The ∆SBP and ∆MAP significantly decreased by two doses of Ach (P
    Conclusion
    These results indicate that nicotinic receptor of the PPT has an inhibitory effect on ∆HR with no significant effect on ∆MAP or ∆SBP.
    Conclusion
    These results indicate that nicotinic receptor of the PPT has an inhibitory effect on ∆HR with no significant effect on ∆MAP or ∆SBP.
    Keywords: Acetylcholine, Blood pressure Hexamethonium, Nicotinic receptor, Pedunculopontine tegmental nucleus
  • Mehmet Erman Erdemli *, Mehmet Gul, Eyup Altinoz, Zeynep Aksungur, Semir Gul, Harika Gozukara Bag Pages 382-387
    Objective(s)
    To investigate protective role of crocin by attempting to create nephrotoxicity with carbon tetrachloride.
    Materials And Methods
    Ethics committee approval was obtained and 50 male Wistar rats were randomly divided into 5 groups that included 10 rats each: Control, Corn oil, Crocin, Carbon tetrachloride (CCl4), and Crocin Carbon tetrachloride. Following the experiments, the rats were decapitated under anesthesia and incised kidney tissues were subjected to biochemical and histological examinations.
    Results
    In the CCl4 administered group, MDA, TOS, Bun, and creatinine levels increased, GSH, SOD, CAT, and TAS levels decreased (P≤0.05), glomerular collapse in kidney sections, narrowing and local occlusion in Bowman’s space in certain glomeruli, inflammatory cell infiltration and congestion were observed when compared to all other groups. There was a significant decrease in increased MDA, TOS, Bun, and creatinine levels, and a significant increase in decreased GSH, SOD, CAT, and TAS levels in CCl4 crocin administered group compared to the CCl4 group (P≤0.05), local minimal glomerular damage, tubular damage, inflammatory infiltration, and vascular collagen symptoms were observed in kidney sections, however significant improvement was observed in damage findings when compared to the CCl4 group.
    Conclusion
    At this dose and time interval, against a highly toxic chemical such as CCl4, crocin was able to suppress oxidative stress by playing a protective role in the kidney tissue.
    Keywords: Crocin, Carbon tetrachloride, Kidney, Oxidative stress, Rat
  • Ezzat Nourizadeh, Seyed Jalal Zargar *, Mohammad Hossein Alimohammadian, Soheila Ajdary, Mehdi Mahdavi Pages 388-394
    Objective(s)
    Leishmaniasis is endemic in 88 countries. Amastigote forms of Leishmania are experts at exploiting host cell processes to establish infection. Monoclonal antibodies are key reagents used in the diagnosis of infectious and non-infectious diseases. The aim of this study was to produce monoclonal antibodies against axenic amastigotes of the Leishmania infantum strain in Iran.
    Materials And Methods
    First, standard strains were cultured and axenic amastigote antigens of L. infantum were obtained. Since then, BALB/c mice were immunized and antibody titers were determined. For hybridoma cell formation, lymphocytes isolated from spleen of immunized mice and myeloma cells were fused at a ratio of 10 to 1 in the presence of polyethylene glycol, followed by limiting dilution for the isolation of monoclones. Subsequently, antibody isotypes were determined by using the isotyping kit. The best clone was injected intraperitoneally to pristane-primed mice for large scale production of monoclonal antibodies. The specificity of antibody was determined with Western blotting.
    Results
    Approximately 25 positive monoclones were obtained, of which four hybrids producing anti-amastigotes L. infantum monoclonal antibodies with high optical density (OD), selected and designated as 8D2 FVI6, 8D2 FVI3, 6G2 FV4 and 6G2 FV3. Results from isotype determination showed the IgG2b sub-class in 6G2FV2 and 8D2FVI6 monoclones.
    Conclusion
    This study produced monoclonal antibody against amastigotes of Iranian strain of L. infantum for the first time. These antibodies have reactivity against Iranian strain of L. infantum and can be used in the diagnosis of Kala-azar.
    Keywords: Axenic amastigotes, Hybridoma cells, Leishmaniases, Leishmania infantum, Monoclonal antibodies
  • Kaveh Rahimi, Javad Sajedianfard *, Ali Akbar Owji Pages 395-399
    Objective(s)
    Calcitonin gene related peptide (CGRP) receptors are widely distributed in the central nervous system. The aim of this study was to investigate the effects of intracerebroventricular (ICV) injection of CGRP on pain behavioral responses and on levels of monoamines in the periaqueductal gray area (PAG) during the formalin test in rats.
    Materials And Methods
    Twenty-four male rats were studied in four groups (n=6). CGRP was injected into the left cerebral ventricle (1.5 nmol, 5 µl). After 20 min, formalin (2.5%) was subcutaneously injected into the right hind paw. Behavior nociceptive score was recorded up to 60 min. During the formalin test, the PAG was subjected to microdialysis and levels of norepinephrine, 3-methoxy-4-hydroxyphenyl-glycol (HMPG), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin and 5-hydroxyindole-acetic acid (HIAA) were measured by HPLC.
    Results
    ICV injection of CGRP lead to a significant pain reduction in acute, middle and chronic phases of the formalin test. Dialysate concentrations of norepinephrine, HMPG, dopamine, DOPAC, serotonin and HIAA in the PGA area showed an increase in acute phase, middle phase and beginning of the chronic phase of the formalin test.
    Conclusion
    CGRP significantly reduced pain by increased concentrations of monoamines and their metabolites in dialysates from PAG when injected ICV to rats.
    Keywords: CGRP, Formalin test, HPLC, Monoamines, Microdialysis
  • Abbas Maleki, Iraj Pakzad * Pages 400-403
    Objective(s)
    The ability of bacteria to produce biofilm and adhesion makes them more resistant to antibiotics. The current study aims to evaluate the biofilm formation by Staphylococcus aureus and to determine the prevalence of adhesion genes, also their correlation with drug resistance.
    Materials And Methods
    A total of 96 MRSA were collected from hospitals of Iran’s western provinces during 2012 to 2013. The presence of ica A,B,C,D,clfA, cna, fnbA, mecA genes were determined by PCR technique. Biofilm formation was studied by microtiter plate assay, the clonal relations of the strains were examined by SCCmec and Spa typing.
    Results
    The results demonstrated that 96 % of isolates were biofilm producers. The distributions of biofilm formation between isolates were 4.2%, 54.2%, 35.4% as high, moderate and weak, respectivelly. The highest biofilm production was observed from blood culture isolates. All virulent genes ica A,B,C,D,clfA, cna, fnbA were observed in moderate and weak biofilm formation isolates. Among high biofilm formation isolates, icaB and cna genes were not seen. Statistical analysis showed that there was a significant correlation between ica, fnbA and the biofilm production, but there was not a significant correlation between the type of samples and drug resistance, spa type and SCCmec type with biofilm production (P>0.05). Frequency of All virulent genes in type III SCCmec was higher than other types.
    Conclusion
    The majority of MRSA isolates were biofilm producers and blood isolates ranked as the great biofilm producer. In these isolates ica D and fnbA genes are correlated with biofilm production.
    Keywords: Antiseptic, Biofilm, MRSA, Resistance genes qacA-B
  • Volkan Gelen *, Emin ?, EngUl, Serkan Yi, Ldi, Rim., G, Ouml, Zde Atila Pages 404-410
    Objective(s)
    5-FU, an anticarcinogenic agent, is reported to have side-effects that include hepatotoxicity and nephrotoxicity. The study objective was to investigate the protective effects of naringin on 5-FU-induced hepatotoxicity and nephrotoxicity.
    Materials And Methods
    Thirty rodents were assigned to three groups. The control group received 1 ml of intragastric distilled water for 14 days. The 5-FU group received 1 ml of distilled water for 14 days as a placebo. On day 9, this same group received a 20 mg/kg dose of 5-FU administered intraperitoneally(IP) for a further five days. The naringinFU group received a 100 mg/kg dose of naringin (IP) for 14 days. On day 9, 20 mg/kg of 5-FU was administered (IP) to this group for a further five days. On day 15, the rats were decapitated, and blood and renal and hepatic tissues were taken.
    Results
    It was determined that serum creatinine, BUN, AST, ALT, ALP, and LDH levels, as well as cytokine levels in the liver and kidney tissues were significantly elevated in the 5-FU group, compared to the control group. The comparative values were similar in the control and naringinFU groups. When the liver tissue was examined histopathologically, in the control group it was found to be normal in structure. However, necrosis was observed in the hepatocytes of the pericentric region in the 5-FU group. 8-OHdG cell density was significantly elevated in the 5-FU group, compared to the control and naringinFU groups.
    Conclusion
    Naringin was observed to have a protective effect on 5-FU-induced liver and kidney damage.
    Keywords: 5-fluorouracil, Hepatotoxicity, Naringin, Nephrotoxicity, Rat
  • Zahra Sabahi, Fatemeh Farmani, Fatemeh Soltani, Mahmoodreza Moein * Pages 411-416
    Objective(s)
    The aim of this study was to prepare fraction and determine the biological activities of the polyphenol-enriched fraction of Berberis integerrima Bunge fruits.
    Materials And Methods
    In this assay fraction was extracted by column chromatography, using Amberlite column as the stationary phase. Phenol and flavonoids in the extract and fraction were analyzed by high performance liquid chromatography (HPLC). DNA protection ability, antioxidant and xanthin oxidase inhibition capacities of this fraction were also examined.
    Results
    Phenol and flavonoid content measurement and HPLC analyses of this fraction confirmed that phenol and flavonoids were increased in fraction in comparison to extract (before using Amberlite column). In antioxidant measurement assay, the trolox equivalent values were 1.05± 0.04 and 0.8±0.11 in oxygen radical absorbance capacity (ORAC) and the EC50 values for cellular antioxidant activity were 55.51±0.21 and 95.67±0.13 µg/ml for quercetin and the fraction, respectively. The xanthin oxidase inhibition percentages were 97.6±0.003 and 90.2 6±0.003 in 100 µg/ml concentration of fraction and Vitamin C respectively. Comet assay analysis showed that this fraction protects human lymphocytes against H2O2-induced DNA damages at 12.5 to 100 µg/ml concentrations.
    Conclusion
    This study suggests that Amberlite column as the stationary phase help to improve phenolic compound in separating fractions. The results showed that B. integerrima fruits are rich in phenolic compounds and they are potent antioxidants with protective effects on oxidative damages. They might be used as functional ingredients in food and supplements.
    Keywords: Antioxidant activity, Berberis integerrima Bunge, Comet assay, DNA protection, Xanthin oxidase inhibitor
  • Razieh Taghizadeh Ghvamabadi, Zahra Taghipour *, Mahsa Hasanipoor, Marzieh Khademi, Mehdi Shariati Pages 417-421
    Objective(s)
    Depression during pregnancy negatively affects fetal development. Fluoxetine as a selective serotonin reuptake inhibitor (SSRIs) is used for treatment of gestational depression. This study is trying to determine the effects of fluoxetine on the renal, heart and lung development.
    Materials And Methods
    Fifteen pregnant rats were treated with fluoxetine at 7 mg/kg from days 0 to 21 of gestation. Immediately after born, heart and kidney samples were evaluated for genes expression and histological assessment. Lung sample were fixed for immunohistochemical study.
    Results
    The gene expression of BMP7 and WNT4 were reduced in the kidney of fluoxetine-treated group (P-value0.05). Histological assessment showed that the glomeruli of the kidneys in treated group are more primordial compared to control. There was a developmental deficiency in Bowman’s capsule, and the capsular space was not clear. The arrangements of the filaments, the position of the nucleus and cells morphology were normal in the hearts of both groups. Immunohistochemical analysis demonstrated that in the fluoxetine-exposed group HoxB5 is more expressed in the mesenchymal cells, but in the control group the expression is limited to alveolar cells.
    Conclusion
    According to developmental changes in kidney, heart and lung, fluoxetine affects neonatal growth during pregnancy, which may lead to delay of some organs growth. So, it is essential to survey the roles of antidepressant drugs on fatal and neonatal development during pregnancy.
    Keywords: Fluoxetine, Heart, Kidney, Lung, SSRIs
  • Yan-Li Wei, Hong-Jian Du, Yi-Ping Lin, Mei-Ling Wu, Ren-Ai Xu * Pages 422-426
    Objective(s)
    In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats, in which a specific probe drug was used for each enzyme.
    Materials And Methods
    After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was 2.0 mg/kg for phenacetin (CYP1A2 activity), 4.0 mg/kg for bupropion (CYP2B6 activity), 2.0 mg/kg for losartan (CYP2C9 activity), 8.0 mg/kg for metoprolol (CYP2D6 activity) and 1.0 mg/kg for midazolam (CYP3A4 activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats’ blood, which were collected at different corresponding times.
    Results
    Our data showed that salidroside exhibited an inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A4 activities by changing the main pharmacokinetic parameters (t1/2, CL/F, Cmax and AUC(0-∞)) of the four probe drugs in rats. However, no significant changes in CYP2D6 activity were observed.
    Conclusion
    In a word, the results displayed that salidroside could induce the activities of CYP1A2, CYP2B6, CYP2C9 and CYP3A4, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic.
    Keywords: Cytochrome P450, Cocktail, Enzyme, Herb-drug interaction, Salidroside
  • Zahra Sadat Hashemi, Mehdi Forouzandeh Moghadam, Samila Farokhimanesh, Masuomeh Rajabibazl, Esmaeil Sadroddiny * Pages 427-433
    Objective(s)
    Various studies have been conducted to reduce the metastatic behavior of cancerous cells. In this regard, ectopic expression of anti-metastatic microRNAs by miR-mimic and miR-restoration-based therapies could bring new insights to the field. In the present study, the consequences of co-transfecting breast cancer cell lines with miR-193b and miR-31 were investigated via invasion and migration assays.
    Materials And Methods
    Double stranded oligonucleotide of mature miR-193b-3p and miR-31-5p were cloned into pcDNA 6.2gw/EmGFP plasmid. The resulting plasmids were used for transfection. Real time-PCR was performed to assess the expression of miR-193b and miR-31 as well as Ras homolog gene family member A (RhoA) and urokinase-type plasminogen activator (uPA) as miR targets. Scratch, Transwell migration and Matrigel invasion assays were carried out to assess the extent of migration and invasion of cell lines.
    Results
    The most significant increase in expression of miRs belonged to the single transfection of mimic-miRs in MDA-MB231. Although the co-transfection was not as successful as single transfection in miR expression, it was significantly more effective in inhibition of the cells invasive potential.
    Conclusion
    Although the miR-restoration therapy based on co-transfection of two miRs could be less effective in expression of each miRNA, the resulting decrease in metastatic behavior of the cells is more significant due to collective effect of co-transfection to decrease target gene expression. Our results revealed that employing this sort of combinatorial strategies could lead to more efficient reduction in metastatic behavior. It seems that using this strategy would bring about more successful therapeutic outcomes.
    Keywords: Breast cancer, Metastasis, miR-31, miR-193b, RhoA, uPA
  • Mohammad Moshiri, Seyed Mojtaba Hosseiniyan, Seyed Adel Moallem, Farzin Hadizadeh, Amir Hosein Jafarian, Ameneh Ghadiri, Toktam Hoseini, Mahmoud Seifi, Leila Etemad * Pages 434-438
    Objective(s)
    Methamphetamine (METH) is a powerful stimulant drug that directly affects the brain and induces neurological deficits. B12 is a water-soluble vitamin (vit) that is reported to attenuate neuronal degeneration. The goal of the present study is to investigate the effect of vitamin B12 on METH’s neurodegenerative changes.
    Materials And Methods
    Two groups of 6 animals received METH (10 mg/kg, interaperitoneally (IP)) four times with a 2 hr interval. Thirty mins before METH administration, vit B12 (1 mg/kg) or normal saline were injected IP. Animals were sacrificed 3 days after the last administration. Caspase proteins levels were measured by Western blotting. Also, samples were examined by TUNEL assay to detect the presence of DNA fragmentation. Reduced glutathione (GSH) was also determined by the Ellman method.
    Results
    The pathological findings showed that vit B12 attenuates the gliosis induced by METH. Vit B12 administration also significantly decreased the apoptotic index in the striatum and the cerebral cortex (P
    Conclusion
    The current study suggests that parenteral vit B12 at safe doses may be a promising treatment for METH-induced brain damage via inhibition of neuron apoptosis and increasing the reduced GSH level. Research focusing on the mechanisms involved in the protective responses of vit B12 can be helpful in providing a novel therapeutic agent against METH-induced neurotoxicity.
    Keywords: Cerebral cortex Methamphetamine Neurotoxicity, Striatum, Vitamin B12