فهرست مطالب

Basic Medical Sciences - Volume:19 Issue:5, 2016
  • Volume:19 Issue:5, 2016
  • تاریخ انتشار: 1395/03/05
  • تعداد عناوین: 15
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  • Alireza Rezaee Khorasany, Hossein Hosseinzadeh* Pages 455-469
    Saffron, the dried red-orange stigmas of Crocus sativus L, has been known as a flavoring agent, food coloring and traditional herbal medicine. Pharmacological effects of saffron are mainly attributed to crocin, crocetin, picrocrocin and safranal. These components especially crocin, have significant effects including antidepressant and anticonvulsant, analgesic, anti-cancer and other therapeutic effects on different parts of our body namely cardiovascular, immune, respiratory, genital-urinary and central nervous system. According to the reports and findings, saffron plays a key role to cure different digestive system disorders via chemopreventive, inhibition of cell proliferation, induction of apoptosis, antioxidant effects and radical scavenging, genoprotective property, prevention of lipid peroxidation and anti-inflammatory processes. The outcome of the above mentioned mechanisms shows potential therapeutic properties of saffron against liver cancer, hepatotoxicity, fatty liver, hyperlipidemia, stomach cancer, peptic ulcer, colon cancer, ulcerative colitis, diabetes and pancreas cancer and ileum contractions. According to global statistics, the susceptibility to intestinal diseases is considered as a significant matter and can be important in health planning in any community. Several strategies for treatment and prevention of the digestive system diseases have provided that the use of herbal remedies seems effective and useful. Considering the available findings, the present study aims to introduce saffron as a prophylactic and therapeutic agent against gastrointestinal tract disorders. However, further clinical studies seem necessary in various aspects of saffron effects in different parts of body to verify these findings.
    Keywords: Crocetin, Crocin, Crocus sativus L, Digestive system, Picrocrocin, Safranal, Saffron
  • Nematollah Ahangar, Zohreh Esam, Ahmadreza Bekhradnia, Mohammad Ali Ebrahimzadeh* Pages 470-475
    Objective(s)
    The mechanism of hypothermia action of acetaminophen (APAP) remains unclear even 125 years after its synthesis. Acetaminophen produces hypothermia. The mechanism of this reduction in core body temperature is not clear but evidence shows that it is not dependent on opioid and cannabinoid receptors. Because of strong documents about the roles of GABA and benzodiazepine receptors in hypothemic activity of some drugs such as diazepam, we determined if these receptors also contributes to the hypothermic effect of APAP.
    Materials And Methods
    Diazepam (5 mg/kg, IP) was used for induction of hypothermia. Flumazenil (10 mg/kg, IP) or picrotoxin (2 mg/kg, IP) used for reversal of this effect. Rats injected with APAP (100, 200 or 300 mg/kg, IP). Baseline temperature measurements were taken with a digital thermometer via rectum. To evaluate the structural correlation between APAP and benzodiazepine receptor ligands, numerous models are selected and studied at HF/6-31G* level of theory. Relative energies, enthalpies and Gibbs free energies were calculated for all selected drugs.
    Results
    Diazepam induced hypothermia was reversed by flumazenil or picrotoxin. Rats injected with APAP displayed dose- and time-related hypothermia. For combined administration, the hypothermic effect of APAP (200 mg/kg) was strongly reduced by pretreatment with picrotoxin or flumazenil P
    Conclusion
    Results suggest hypothermic action of acetaminophen may be mediate by its effect at GABAA benzodiazepine receptor.
    Keywords: Abinitio study, Acetaminophen, Benzodiazepine receptor, Hypothermia, GABAA
  • Shokoufeh Aalaei, Hadi Shahraki, Alireza Rowhanimanesh, Saeid Eslami* Pages 476-482
    Objective(s)
    This study addresses feature selection for breast cancer diagnosis. The present process uses a wrapper approach using GA-based on feature selection and PS-classifier. The results of experiment show that the proposed model is comparable to the other models on Wisconsin breast cancer datasets.
    Materials And Methods
    To evaluate effectiveness of proposed feature selection method, we employed three different classifiers artificial neural network (ANN) and PS-classifier and genetic algorithm based classifier (GA-classifier) on Wisconsin breast cancer datasets include Wisconsin breast cancer dataset (WBC), Wisconsin diagnosis breast cancer (WDBC), and Wisconsin prognosis breast cancer (WPBC).
    Results
    For WBC dataset, it is observed that feature selection improved the accuracy of all classifiers expect of ANN and the best accuracy with feature selection achieved by PS-classifier. For WDBC and WPBC, results show feature selection improved accuracy of all three classifiers and the best accuracy with feature selection achieved by ANN. Also specificity and sensitivity improved after feature selection.
    Conclusion
    The results show that feature selection can improve accuracy, specificity and sensitivity of classifiers. Result of this study is comparable with the other studies on Wisconsin breast cancer datasets.
    Keywords: Breast cancer, Classification feature, Selection data mining
  • Murat Karamese*, Bulent Guvendi, Selina Aksak Karamese, Irfan Cinar, Serpil Can, Huseyin Serkan Erol, Hakan Aydin, Volkan Gelen, Emre Karakus Pages 483-489
    Objective(s)
    In the present study, our aim was to investigate the possible protective effects of epigallocatechin gallate (EGCG) on lipopolysaccharide (LPS)-induced hepatotoxicity by using Hep3B human hepatoma cells. Specifically, the study examines the role of some proinflammatory markers and oxidative damage as possible mechanisms of LPS-associated cytotoxicity. Consequently, the hepatocellular carcinoma cell line Hep3B was chosen as a model for investigation of LPS toxicity and the effect of EGCG on LPS-exposed cells.
    Materials And Methods
    The Hep3B human hepatoma cells were used for this study. The cytotoxic effects of chemicals (EGCG and LPS), AST and ALT levels, SOD and CAT activities, GSH-Px level and TNF-alpha and IL-6 levels were detected by using different biochemical and molecular methods. LPS and EGCG were applied to cells at various times and doses.
    Results
    The highest treatment dose of EGCG (400 µM) led to a dramatic decrease in SOD level and increase in CAT and GSH levels. Additionally, the highest dose of EGCG also led to a dramatic increase in TNF-alpha and IL-6 levels. On the other hand, effective doses of EGCG (200 and 100 µM) normalized all related parameters levels.
    Conclusion
    LPS caused hepatotoxicity, but interestingly, a high dose of EGCG was found to be a cytotoxic agent in this study. However, other two doses of EGCG led to a decrease in both inflammatory cytokine levels and antioxidant enzyme levels. Further studies should examine the effect of EGCG on secondary cellular signaling pathways.
    Keywords: Cytokines, Epigallocatechin gallate, Hep3B, Lipopolysaccharide Oxidative stress
  • Afshin Kheradmand, Alireza Mohajjel Nayebi, Masoumeh Jorjani, Rasool Haddadi Pages 490-496
    Objective(s)
    Neuroinflammation and oxidative stress play a key role in pathogenesis of Parkinson’s disease (PD). In the present study we investigated the effect of reactive oxygen species (ROS) scavenger WR-1065 on catalepsy and cerebrospinal fluid (CSF) level of interleukin 6(IL-6) and striatum superoxide dismutase (SOD) activity in 6-hydroxydopamine (6-OHDA) induced experimental model of PD.
    Materials And Methods
    Seventy two male Wistar rats were divided into 9 equal groups and 6-OHDA (8 μg/2 μl/rat) was infused unilaterally into substantia nigra pars copmacta (SNc) to induce PD. Catalepsy was measured by standard bar test, CSF level of IL-6 was assessed by enzyme-linked immunosorbent assay (ELISA) method and SOD activity measured by spectrophotometric method. In pre-treatment groups WR-1065 (20, 40 and 80 μg/2 μl/rat/day, for 3 days) was infused into the SNc before 6-OHDA administration and 21 days later, as a recovery period, behavioral and molecular assay tests were done.
    Results
    Our results showed that pre-treatment with WR-1065 improved (P
    Conclusion
    Our study indicated that pre-treatment with WR-1065 could modulate catalepsy and IL-6 level in 6-OHDA-lesioned rats. Also WR1065 could increase SOD activity up to normal range. It can be regarded as an anti-oxidative drug in prevention or adjunctive therapy of PD.
    Keywords: Catalepsy, IL, 6, Rat, SOD, WR, 1065
  • Song Liu*, Zhonghua Wang, Bo Xu, Kui Chen, Jinyuan Sun, Lianping Ren Pages 497-802
    Objective(s)
    Intermittent hypoxia (IH), caused by obstructive sleep apnea (OSA), could cause hippocampus or neuron damage through multiple signaling pathways, while the underlying mechanisms are still unclear. Thus, the present study aimed to explore the effect of IH on the biological functions of microglia cells.
    Materials And Methods
    Cell proliferation of BV2 cells after exposure to IH were observed by MTT assay and then DNA damage was detected by comet assay. RNA-sequencing assay was performed in cells under IH condition and normal conditions to find out the differentially expressed genes, which were further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot assay.
    Results
    As results, IH inhibited the proliferation of BV2 cells, as well as caused DNA damage. RNA-sequencing assay revealed 4 differentially expressed genes (p21, Cyclin D1, Cyclin E2, and Gadd45α) which were associated with the network of P53 signaling pathways in BV2 cells, among which, p21 and Gadd45α were dramatically increased while Cyclin D1 and Cyclin E2 were both decreased significantly. Moreover, inflammatory factors including IL-6, TNF-α and iNOS were significantly up-regulated in microglia cells under IH conditions for 8 hr.
    Conclusion
    Our results indicated that IH could inhibit cyclin D1 and cyclin E2 expression via initiating multiple P53 pathways, which further blocked cell cycle transition and attenuated proliferative capability of BV2 cells. Meanwhile, IH activated inflammation reactions in BV2 cells. Present study elaborate the effects of IH on biological functions of microglia and provide theoretical foundation for further study on new therapy methods for OSA.
    Keywords: Inflammatory cytokine, Intermittent hypoxia, Microglia, P53 signaling pathways
  • Mahdi Mojarrab, Mehran Mehrabi, Farahnaz Ahmadi, Leila Hosseinzadeh* Pages 803-810
    Objective(s)
    This study was designed to indicate whether different fractions from Artemisia biennis hydroethanolic extract could provide cytoprotection against oxidative stress and apoptosis induced by doxorubicin (DOX) in rat pheochromocytoma cell line (PC12).
    Material and
    Methods
    Cell viability was determined by MTT assay. Also, activation of caspase-3 and superoxide dismutase were evaluated by spectrophotometry. Detection of reactive oxygen species (ROS) and measurement of mitochondrial membrane potential (MMP) were performed by flowcytometry.
    Results
    Treatment of PC12 cells with DOX reduced viability dose dependently. For evaluation of the effect of fractions (A-G) on DOX-induced cytotoxicity, PC12 cells were pretreated for 24 hr with the A. biennis fractions and then cells were treated with DOX. The fractions C and D increased PC12 cells viability significantly compared to DOX treated cells. Moreover, pretreatment with fractions C and D for 24 hr attenuated DOX-mediated apoptosis and the anti-apoptotic action of A. biennis fractions was partially dependent on inhibition of caspase 3 activity and also increasing the mitochondrial membrane potential (MMP). Selected A. biennis fractions also suppressed the generation of ROS and increased superoxide dismutase (SOD) activity.
    Conclusion
    Taken together our observation indicated that subtoxic concentration of aforementioned fractions of A. biennis hydroetanolic extract has protective effect against apoptosis induced by DOX in PC12 cell. The results highlighted that fractions C and D may exert cytoprotective effects through their antioxidant actions.
    Keywords: Apoptosis, Artemisia biennis, Doxorubicin, Oxidative stress, PC12 cell line
  • Oyelowo Oluwakemi*, Adegoke Olufeyisipe Pages 811-820
    Objective(s)
    The aim of this study was to evaluate the oxidative status and DNA integrity in testes of wistar rat offspring exposed to omega-9 monounsaturated (MUFA) at different times of late organogenesis.
    Materials And Methods
    Sixty female rats were divided into six groups of 10 animals. The first group served as control and received the drug vehicle, olive oil (1 ml/kg/day). The second, third, fourth, fifth and sixth group received 1000 mg/kg of oleic acid on gestation day 15 (D15), 16 (D16), 17 (D17), 18 (D18) and 19 (D19), respectively. Male pups were allowed to attain puberty and thereafter, blood was taken for hormonal analyses. Sperm count and motility were assessed. Testes homogenate was used for the determination of biochemical variables. Testes DNA was also determined.
    Results
    The results showed that sperm count and motility were significantly decreased in the treated groups as compared to the control. There was a marked increase in the malondialdehyde level in rat testes from all of the treated groups as compared to the control (P
    Conclusion
    Omega-9 MUFA exposure in utero imposes negative effects on sperm variables and increases the level of sperm DNA fragmentation and oxidative stress.
    Keywords: Deoxyribonucleic acid, Oleic acid, Oxidative stress, Superoxide dismutase, Total protein
  • Seung Min Park, Jae, Chul Lee, Bai Hui Chen, Bich, Na Shin, Jeong Hwi Cho, In Hye Kim, Joon Ha Park, Moo, Ho Won, Ji Hyeon Ahn, Hyun, Jin Tae, Myoung Cheol Shin, Chan Woo Park, Jun Hwi Cho, Hui Young Lee* Pages 821-828
    Objective(s)
    The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region.
    Materials And Methods
    Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry.
    Results
    About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion.
    Conclusion
    CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults.
    Keywords: CA1 region, Delayed neuronal death, Ischemia, reperfusion injury Pyramidal neurons, Young gerbil
  • Davoud Salarbashi, Samaneh Attaran Dowom, Bibi Sedigheh Fazly Bazzaz, Farhad Khanzadeh*, Vahid Soheili, Ali Mohammadpour Pages 829-841
    Objective(s)
    To optimize the extraction method using response surface methodology, extract the phenolic compounds, and identify the antioxidant and biological properties of Stachys parviflora L. extracts.
    Materials And Methods
    Maceration and ultrasound-assisted extraction (UAE) (4, 7, 10 min treatment time, 40, 70, 100 % high-intensity and 60, 80, 100 % (v v-1) methanol purity) were applied to obtain the extracts. SEM was conducted to provide the microstructure of the extracted plant. MICs (colorimetric assay), MFCs (colony diameter), total phenolic content, total flavonoid content, radical scavenging capacity and extraction efficiency were determined. HPLC analysis was applied to measure the existent phenolic compounds.
    Results
    A quadratic model (4 min treatment time, 74.5 % high-intensity and 74.2 % solvent purity) was suggested as the best (TPC: 20.89 mg GAE g-1 d.m., TFC: 6.22 mg QEs g-1 d.m., DPPH IC50: 21.86 µg ml-1 and EE: 113.65 mg g-1 d.m.) UAE extraction model. The optimized UAE extract was generally more effective against Gram-positive microorganisms (MIC: 10-20; MBC: 10-40 (mg ml-1)) than Gram-negative ones (MIC: 40; MBC: >40 (mg ml-1)). Moreover, it (MGI: 2.32-100 %) revealed more anti-mold activity than maceration (MGI:
    Conclusion
    RSM optimization was successfully applied for UAE from S. parviflora. The considerable antioxidant and biological properties were attributed to the phenolic compounds.
    Keywords: Antioxidant, Biological properties, HPLC, RSM, Stachys parviflora L, UAE
  • Neda Soliemani, Alireza Moslem, Ali Shamsizadeh, Hassan Azhdari, Zarmehri* Pages 842-849
    Objective(s)
    Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA).
    Materials And Methods
    Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive responses were measured by formalin test (50 µl injection of formalin 2% subcutaneously into hind paw) and, pain related behaviors were monitored for 90 min following intra-microinjection of SB-334867 (orexin receptor 1 antagonist) into RVM.
    Results
    Exposure to swimming stress test after administration of SB-334867 into RVM significantly reduces the formalin-induced nociceptive behaviors in phase1, interphase, and phase 2 in rats.
    Conclusion
    The result demonstrated the involvement of OXR1 in antinociceptive behaviors induced by swim stress in RVM.
    Keywords: Formalin test, Orexin receptors, Rostral ventromedial medulla, Stress induced analgesia
  • Saieede Soltani, Parvin Zakeri, Milani, Mohammad Barzegar, Jalali, Mitra Jelvehgari* Pages 850-860
    Objective(s)
    Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H1-receptor) that is used topically in the treatment of allergic conditions of rhinitis and conjunctivitis. The aim of this study was to formulate and improve an ophthalmic delivery system of KF.Ocular nanoparticles were prepared with the objective of reducing the frequency of administration and obtaining controlled release to improve the anti-inflammatory drug delivery.
    Materials And Methods
    In the present study, ocular KF loaded Eudragit RL 100 nanoparticles were prepared using O/W solvent diffusion method. The nanoparticles were evaluated for particle size, entrapment efficiency, surface morphology, X-ray diffraction (XRD), Fourier transform spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro release and permeation studies were also carried out on nanoparticles.
    Results
    An average size range of 182 to 314.30 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Drug release for all formulations after 24 hr was between 65.51% and 88.82% indicating effective controlled release property of KF. The mechanism of drug release for best formulation was found to be fickian diffusion mechanism. KF nanoparticles containing high polymer concentration (1:15) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (1:7.5) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea.
    Conclusion
    The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability.
    Keywords: Eudragit RL 100, Ketotifen fumarate, Nanoparticle, Ocular
  • Haikuo Xue, Huijun Ren, Lei Zhang, Xiaoxu Sun, Wanhai Wang, Shijie Zhang, Junwei Zhao, Liang Ming* Pages 861-866
    Objective(s)
    Multiple sclerosis (MS) is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E) is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and treated EAE with α-tocopherol (AT) which is the main content of Vit E.
    Materials And Methods
    Twenty C57BL/6 adult female mice were used and divided into two groups randomly. EAE was induced with myelin oligodendrocyte glycoprotein (MOG), and one group was treated with AT, at a dose of 100 mg/kg on the 3th day post-immunization with MOG, the other group was treated with 1% alcohol. Mice were euthanized on day 14, post-immunization, spleens were removed for assessing splenocytes proliferation and cytokine profile, and spinal cords were dissected to assess the infiltration of inflammatory cells in spinal cord.
    Results
    AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine), though the other cytokines were only affected slightly.
    Conclusion
    According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS.
    Keywords: Alpha, tocopherol, Autoimmunity, Inammation, Multiple sclerosis, Vitamin E
  • Dongming Zheng, Lijuan Zhang, Quan Na, Sishi Liu, Yanyan Zhuang, Yuan Lv, Caixia Liu* Pages 867-872
    Objective(s)
    We aimed to investigate the influence of transient receptor potential channel 3 (TRPC3) on lipopolysaccharide-induced (LPS) preterm delivery mice.
    Materials And Methods
    Mice were randomly assigned to the four groups: an unpregnant group, a mid-pregnancy group (E15), a term delivery group, and an LPS-induced preterm delivery group (intraperitoneal injection LPS at 15 days). Uterine smooth muscles were obtained through caesarean section; TRPC3 expression was measured by real-time PCR, western blotting, and immunohistochemistry. A specific inhibitor of TRPC3 (SKF96365) was injected into the LPS-induced preterm delivery group to determine whether the delivery interval was prolonged.
    Results
    TRPC3 was primarily expressed in the uterine smooth muscle layer. In addition, the LPS-induced preterm delivery group had an obviously higher expression level of TRPC3 mRNA and protein compared with the unpregnant and E15 groups, which were close to term delivery. More importantly, SKF96365 prolongs the delivery interval of LPS-induced preterm delivery mice.
    Conclusion
    Enhanced expression of TRPC3 may be associated with LPS-induced preterm delivery in mice. The specific inhibitor of TRPC3 (SKF96365) may be helpful for clinical treatment of preterm delivery.
    Keywords: Preterm delivery, SKF96365, TRPC3, Uterine muscle
  • Yang Mei, Zhuang Yangyang, Luo Shuai, Jin Hao, Yang Yirong, Cai Yong, Xia Peng, Chen Bicheng, Zhang Yan* Pages 873-878
    Objective(s)
    Our recent report indicates that breviscapine play a protective role of the kidney by down-regulating transforming growth factor-β1(TGF-β1), α-smooth muscle actin (α-SMA) and alleviating interstitial fibrosis following unilateral ureteral obstruction (UUO). In this study, we investigate the effect of breviscapine on changes of renal water and sodium transport proteins in response to UUO.
    Materials And Methods
    Male Sprague-Dawley rats were divided into 3 groups, sham group, UUO group and UUO treat with breviscapine. After 4, 7 and 14 days, histologic changes and interstitial collagen were determined microscopically following hematoxylin and eosin (H&E) and Masson's trichrome staining. The expression of Aquaporins (AQP-2) and γ-epithelial sodium channel (γ-ENaC) were investigated using immunohistochemistry and Western blot in each group.
    Results
    Breviscapine treatment decrease the tubular injury index and the degree of interstitial collagen deposition significantly compared with the UUO group (P
    Conclusion
    These results demonstrate that breviscapine could prevent downregulation of renal water and sodium transport proteins in response to UUO so as to protect obstructed kidney.
    Keywords: Antioxidant, Biological properties, HPLC, RSM, Stachys parviflora L, UAE