فهرست مطالب

Basic Medical Sciences - Volume:23 Issue: 3, 2020
  • Volume:23 Issue: 3, 2020
  • تاریخ انتشار: 1398/11/02
  • تعداد عناوین: 17
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  • Arezoo Rajabian, Hamid Reza Sadeghnia, Sahar Fanoudi, Azar Hosseini * Pages 277-286

    Neurodegenerative diseases, characterized by progressive loss of neurons, share common mechanisms such as apoptotic cell death, mitochondrial dysfunction, inflammation, and oxidative stress. Genus Boswellia is a genus in the Burseraceae family. It comprises several species traditionally used for treatment of chronic inflammatory diseases, cerebral edema, chronic pain syndrome, gastrointestinal diseases, tumors, as well as enhancing intelligence. Many studies have been carried out to discover therapeutic approaches for neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic lateral sclerosis, stroke, and concomitant cognitive deficits. However, no curative treatment has been developed. This paper provides an overview of evidence about the potential of the Boswellia species and their main constituents, boswellic acids, as modulators of several mechanisms involved in the pathology of the neurodegenerative diseases. In vitro, animal, and clinical studies have confirmed that Boswellia species contain bioactive components that may enhance cognitive activity and protect against neurodegeneration. They exert the beneficial effects via targeting multiple pathological causes by antioxidative, anti-inflammatory, antiamyloidogenic, and anti-apoptotic properties. The Boswellia species, having neuroprotective potential, makes them a promising candidate to cure or prevent the neurodegenerative disorders.

    Keywords: Alzheimer’s diseases, Boswellia, Cognitive, Neurodegenerative diseases, Neuroprotection
  • Tahereh Kalantari, Bogoljub Ciric, Eskandar Kamali Sarvestani, Abdolmohamad Rostami * Pages 287-292
    Objective(s)

    In addition to pro-inflammatory role, dendritic cells (DCs) can also be anti-inflammatory when they acquire tolerogenic phenotype. In this study we tested the role of CD40 and IL-23p19 in antigen presenting function of bone marrow-derived DCs (BMDCs) by comparing BMDCs derived from CD40 knockout (CD40KO-DCs) and IL-23p19 (IL-23p19KO-DCs) knockout mice with those from C57BL/6 mice (Cont-DCs). We have focused on CD40 and IL-23, as these molecules have well established pro-inflammatory roles in a number of autoimmune and inflammatory diseases.

    Materials and Methods

    The expression of maturation markers MHC II and co-stimulatory molecules CD40, CD80, and CD86 was analyzed by flow cytometry, while the expression of CD40 and IL-23p19 was measured by RT-PCR. The capacity of BMDCs to activate CD4+ T cells was evaluated by 3H-thymidine incorporation, and the capacity of BMDCs to uptake antigen was evaluated using fluorescent OVA and flow cytometry.

    Results

    The lack of CD40 or IL-23p19 had no effect on uptake of FITC-OVA by the DCs, confirming their immature phenotype. Moreover, CD40KO-DCs had significantly reduced capacity to stimulate proliferation of CD4+ T cells. CD4+ T cells activated by CD40KO-DCs and IL-23p19KO-DCs produced significantly less IFN-γ (P-value ≤0.05), while CD4+ T cells stimulated by IL-23p19KO-DCs produced less GM-CSF and more IL-10 than Cont-DCs.

    Conclusion

    This study shows that CD40KO-DCs and IL-23p19KO-DCs have a marked tolerogenic potency in vitro. Future in vivo studies should determine if and to what extent DCs lacking CD40 or IL-23 have a potential to be useful in therapy of autoimmune inflammation.

    Keywords: CD40, CD40KO, IL-23, IL-23p19KO, Tolerogenic DC
  • Atefeh Hemati, Mohammad Hossein Modarressi, Sedighe Kolivand, Mahnaz Azarnia * Pages 293-297
    Objective(s)
    Here, we examined the function of our produced monoclonal antibody (mAb10C3) to recognize one of the most important members of the HEAT shock factor family, Hsf5, in embryonic development and in spermatogenic cells of adult mouse testis.
    Materials and Methods
    The targeting effects of mAb10C3 were investigated by immunohistochemistry analysis in the different phases of the embryo and in the adult testis tissue sections.
    Results
    The results of immunohistochemistry staining on the mouse embryos by the supernatant of hybridoma clone that produced mAb10C3, in the early and late phases (E7.5 and E14.5) of embryonic development, indicated that mAb10C3 could only detect Hsf5 in E7.5 and it did not have any targeting activity in the late phase of development. Therefore, we showed that the hsf5 gene has expressed in early mouse embryonic development. On the other hand, mAb10C3 could detect Hsf5 in spermatogonia and spermatocytes of adult testis in comparison with a known anti-Hsf5 antibody (ab98939) and an anti-PCNA antibody as a marker of spermatogonia cells.
    Conclusion
    Taken together, these data indicated that generated anti-testis mAb10C3 was generated against anti-testis proteins, specifically to target Hsf5, and can be useful as a scientific tool to investigate the critical genes in the development and spermatogenesis.
    Keywords: antibody, Development, Hsf5, Hybridoma, Spermatogenesis
  • Ke Li, Yuran Zhou, Bao Fu * Pages 298-302
    Objective(s)
    Melatonin, an important hormone secreted by the epiphysis, is a powerful anti-oxidant with a high potential to neutralize medical toxins. The goal of this study was to demonstrate the beneficial effect of melatonin on epididymal sperm and reproductive parameters in mice treated with acetylsalicylic acid (ASA).
    Materials and Methods
    Thirty-nine SD rats were randomly split into D1 receptor agonist (chloro-APB), D1 receptor antagonist (SCH23390), and saline groups after preparing NB microinjection model. We observed the effect of NB microinjection of SCH23390, chloro-APB, or saline on the period of induction and recovery time of propofol anesthesia and recorded the changes of electroencephalogram (EEG) simultaneously.
    Results
    NB microinjection of chloro-APB accelerated the recovery from propofol anesthesia (P<0.05), without affecting the induction of anesthesia (P>0.05); NB microinjection of SCH23390 produced the opposite effects. NB microinjection of saline did not influence the induction or recovery of propofol anesthesia (P>0.05). NB injection of chloro-APB decreased the ratio of δ power and increasedαand β ratios in prefrontal cortex EEG (P<0.05); NB microinjection of SCH23390 increased δ ratio and decreased β ratio (P<0.05); NB microinjection of saline had no significant effect on EEG (P>0.05).
    Conclusion
    D1 dopamine receptors in NB are involved in modulating the emergence from propofol anesthesia, but not affecting the induction of propofol anesthesia.
    Keywords: Dopamine d1 receptors, Emergence, Induction, Nucleus Basalis, Propofol
  • Seyedeh Farzaneh Omidkhoda, Marjan Razavi, Mohsen Imenshahidi, Maryam Rameshrad, Hossein Hosseinzadeh * Pages 303-310
    Objective(s)
    One of the most important problems of taking nitroglycerin is the nitrate tolerance phenomenon and endothelial dysfunction. Oxidative stress is a high-emphasized one of tolerance mechanisms. The possible effect of crocin, one of the anti-oxidant ingredients of saffron, on the nitrate tolerance model was investigated.
    Materials and Methods
    In the present study, lipid peroxidation and the level of activated and deactivated forms of eNOS were measured. Animals were administered subcutaneously with 25 mg/kg of nitroglycerin, twice a day for 3 days to induce nitrate tolerance model. For evaluation of crocin effects, 20, 40 and 80 mg/kg/day of this compound were injected intraperitoneally in concomitant with nitroglycerin. In the isolated aorta test, after preparation of aorta rings, different concentrations of acetylcholine, sodium nitroprusside and nitroglycerin were added to the organ bath after inducing contraction by phenylephrine and the responsiveness of tissues was recorded.
    Results
    Findings showed that nitroglycerin administration caused a remarkable overproduction of malondialdehyde (MDA) in the cells and crocin treatment significantly decreased the MDA level. In the nitrate tolerance group, the level of activated eNOS decreased and the level of deactivated eNOS increased. Crocin partly alleviated these changes: however, its effects were not remarkable. Nitroglycerin injection for 3 days developed tolerance to nitroglycerin and cross-tolerance to acetylcholine (endothelial dysfunction) and sodium nitroprusside. Crocin failed to influence significantly on the nitrate tolerance.
    Conclusion
    Crocin effectiveness is possibly time-dependent; therefore, increasing the duration of treatment with crocin may lead to a significant prevention of nitrate tolerance and endothelial dysfunction.
    Keywords: Crocin, Endothelial dysfunction, Malondialdehyde, Nitrate tolerance, Oxidative stress
  • Mohammad Pouralijan Amiri, Maryam Khoshkam, Reza Madadi, Koorosh Kamali, Ghassem Faghanzadeh Ganji, Reza Salek, Ali Ramazani * Pages 311-320
    Objective(s)
    Unstable angina (UA) is a form of the acute coronary syndrome (ACS) that affects more than a third of the population before age 70. Due to the limitations of diagnostic tests, appropriate identification of UA is difficult. In this study, we proceeded to investigate metabolite profiling in UA patients compared with controls to determine potential candidate biomarkers.
    Materials and Methods
    Ninety-four plasma samples from UA and 32 samples from controls were analyzed based on 1H NMR spectroscopy. The raw data were processed, analyzed, and subjected to partial least squares-discrimination analysis (PLS-DA), a supervised classification method with a good separation of control and UA patients was observed. The most important variables (VIP) ≥1 were selected and submitted to MetaboAnalyst pathway enrichment to identify the most important ones.
    Results
    We identified 17 disturbed metabolites in UA patients in comparison with the controls.   These metabolites are involved in various biochemical pathways such as steroid hormone biosynthesis, aminoacyl-tRNA biosynthesis, and lysine degradation. Some of the metabolites were deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, androstanedione, etiocholanolone, estradiol, 2-hydroxyestradiol, 2-hydroxyestrone, 2-methoxyestradiol, and 2-methoxyestrone. In order to determine test applicability in diagnosing UA, a diagnostic model was further created using the receiver operator characteristic (ROC) curve. The areas under the curve (AUC), sensitivity, specificity, and precision were 0.87, 90%, 65%, and 91%, respectively, for diagnosing of UA.
    Conclusion
    These metabolites could not only be useful for the diagnosis of UA patients but also provide more information for further deciphering of the biological processes of UA.
    Keywords: Biomarker, Metabolites, Metabolomics, NMR spectroscopy, Unstable angina
  • Emad Khademi, Vahid Pirhajati Mahabadi, Hassan Ahmadvand, Esmaeil Akbari, Alireza Khalatbary * Pages 321-328
    Objective(s)
    Cisplatin-induced peripheral neuropathy is a debilitating side effect in patients receiving this drug.  Recent studies suggest hyperbaric oxygen (HBO) therapy as a new treatment approach for models of neural injury. The aim of the current study was to determine the protective effects of HBO preconditioning against peripheral neuropathy induced by Cisplatin (CDDP).
    Materials and Methods
    The present study was conducted on 4 groups of rats: Sham group; HBO group (60 min/d); Control group (CDDP 2 mg/kg/d); Precondition group (HBO+CDDP). Mechanical threshold testing was weekly carried out using von Frey filament. Sciatic nerve and associated ganglia were removed  five weeks after the first CDDP injection for biochemical evaluation of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity, immunohistochemistry of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), TNF-α, caspase-3 and  iNOS, and transmission electron microscopic (TEM) assessments.
    Results
    MDA levels and MPO activities were significantly decreased in preconditioned rats. Attenuated TUNEL reaction along with attenuated caspase-3, TNF-α, and iNOS expression could be significantly detected in preconditioned rats. Also, HBO preconditioning improved the nociceptive threshold.
    Conclusion
    The results suggest that HBO preconditioning can attenuate peripheral neuropathy caused by cisplatin in rats.
    Keywords: Apoptosis, Cisplatin, Hyperbaric oxygen, Inflammation, Neuropathy
  • Jing Zhang, Zhi Qiang Xue, Bin Wang, Jia Xin Wen, Yun Xi Wang * Pages 329-336
    Objective(s)

    To investigate the role of miR-22 in the efficacy of combined icotinib (BPI-2009H) and pemetrexed (LY-231514) on tumor growth and apoptosis in rats with non-small cell lung cancer (NSCLC).

    Materials and Methods

    Rats were injected with HCC827 cells, which were transfected with anti-miR-22, followed by the treatment of BPI-2009H and/or LY-231514. MTT assay was used to detect the inhibition rate of HCC827 cells. qRT-PCR was performed to examine miR-22 expression in HCC827 cells and lung tumor tissues. Moreover, immunohistochemistry and Western blotting were performed to detect the related-molecule expressions, while TUNEL staining was used to observe cell apoptosis of lung tumor tissues.

    Results

    MiR-22 expression was decreased in HCC827 cells after the treatment of BPI-2009H or LY-231514 in a dose-dependent manner. Both BPI-2009H and LY-231514 increased the inhibition rate of HCC827 cells, which was enhanced by anti-miR-22 with decreased IC50 values. Furthermore, the decreased expression of miR-22 was found after the treatment of BPI-2009H or/and LY-231514 in lung tumor tissues. In addition, the expressions of PCNA, Ki67, and Bcl-2 were reduced, but Bax and Caspase-3 were increased in treated rats, typically in those rats treated with the combination of anti-miR-22, BPI-2009H, and LY-231514.

    Conclusion

    Inhibition of miR-22 could enhance the efficacy of icotinib combined with pemetrexed in rats with NSCLC, providing a new perspective for NSCLC therapy.

    Keywords: Carcinoma, Human, Icotinib, MIRN22 microRNA, Non-Small-Cell Lung, Pemetrexed
  • Susan Sarhadi, Mostafa Gholizadeh, Tina Moghadasian, Shiva Golmohamadzadeh * Pages 337-343
    Objective(s)
    The present study aimed to determine and compare moisturizing and occlusion effects of different solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using magnetized water and deionized water.
    Materials and Methods
    SLN formulations were prepared using various lipids, including Tripalmitin, Compritol®, Precirol®, and emulsifiers including Poloxamer and Tween 80. NLC formulations were also prepared with oleic acid and the same solid lipids. Two types of formulations were prepared; first with deionized water and then with magnetized water. Formulations were prepared using high shear homogenization and ultrasound methods. The products were analyzed by PSA (particle size analyzer), DSC (differential scanning calorimetry), and TEM (transmission electron microscopy). The moisturizing effect of formulations was determined by in vivo and in vitro methods.
    Results
    Findings of the assessments demonstrated that in products prepared with magnetized water, 5% SLN Precirol® had the most moisturizing effect in vivo and 5% SLN Compritol® had the most moisturizing effect in vitro. The use of magnetized water in formulations can improve the effectiveness and increase the stability of moisturizing products.
    Conclusion
    In this study, all products prepared with magnetized water showed more stability, smaller size, and more moisturizing effects compared with products prepared with deionized water.
    Keywords: Deionized water, Magnetized water, NLC, Skin dryness, SLN
  • Abolfazl Akbari, Gholamali Jelodar * Pages 344-353
    Objective(s)
    Resistin, as a 12.5 kDa cysteine-rich polypeptide, is expressed in hypothalamus and regulates sympathetic nerve activity. It is associated with obesity, metabolic syndrome and cardiovascular diseases. In this study, we investigated the neural pathway of cardiovascular responses induced by injection of resistin into paraventricular nucleus (PVN) with rostral ventrolateral medulla (RVLM).
    Materials and Methods
    Adult male rats were anesthetized with urethane (1.4 g/kg intraperitoneally). Resistin (3 µg/1 µl/rat) was first injected into PVN, and the glutamatergic, corticotrophin-releasing factor (CRF)-ergic and angiotensinogenic transmission was inhibited by injecting of their antagonist in RVLM. Arterial pressure (AP) and heart rate (HR) were monitored before and after the injection.
    Results
    The results showed that resistin injection into PVN significantly increased AP and HR compared to control group and prior to its injection (P<0.05). Injection of AP5 ((2R)-amino-5-phosphonovaleric acid; (2R)-amino-5-phosphonopentanoate) (50 nM/rat), losartan (10 nM/rat) and astressin (50 nM/rat) into RVLM reduced cardiovascular responses produced by injected resistin into PVN. Injection of AP5+losartan or astressin+losartan or astressin+AP5 into RVLM could significantly reduce cardiovascular responses produced by resistin compared to before injection (P<0.05). Furthermore, the depressor responses generated by AP5+losartan injected into RVLM were significantly stronger than the depressor responses generated by AP5+astressin and/or astressin+losartan injected into RVLM (P<0.05).
    Conclusion
    It can be concluded that glutamatergic and CRFergic transmissions have crucial contribution to cardiovascular responses produced by resistin. The results provided new and potentially important insight regarding neural transmission when the plasma level of resistin increases; this reveals the role of resistin in cardiovascular responses such as metabolic syndrome and hypertension.
    Keywords: Angiotensin II, Arterial Pressure, Corticotrophin-releasing hormone, Heart rate, L-Glutamate, Paraventricular hypothalamic nucleus, Resistin
  • Sara Abdollahi, Azizollah Khodakaram Tafti, Hadi Aligholi, Saeid Ziaei, Maryam Khaleghi Ghadiri, Walter Stummer, Ali Gorji * Pages 354-361
    Objective(s)

    Neural stem/progenitor cells (NS/PCs) hold a great potential for delivery of therapeutic agents into the injured regions of the brain. Efficient gene delivery using NS/PCs may correct a genetic defect, produce therapeutic proteins or neurotransmitters, and modulate enzyme activation. Here, we investigated the efficiency of a recombinant lentivirus vector expressing green fluorescent protein (GFP) for genetic engineering of human NS/PCs obtained during brain surgery on patients with medically intractable epilepsy.

    Materials and Methods

    NS/PCs were isolated from human epileptic neocortical tissues. Three plasmids (pCDH, psPAX2, pMD2.G) were used to make the virus. To produce the recombinant viruses, vectors were transmitted simultaneously into HEk-293T cells. The lentiviral particles were then used to transduce human NS/PCs.

    Results

    Our in vitro study revealed that lentivirus vector expressing GFP efficiently transduced about 80% of human NS/PCs. The expression of GFP was assessed as early as 3 days following exposure and remained persistent for at least 4 weeks.

    Conclusion

    Lentiviral vectors can mediate stable, long-term expression of GFP in human NS/PCs obtained from epileptic neocortical tissues. This suggests lentiviral vectors as a potential useful tool in human NS/PCs-based gene therapy for neurological disorders, such as epilepsy.

    Keywords: GFP, Lentivirus, Neural stem, progenitor cells, Seizure, Transplantation
  • Yun Mei Zhang, Zhen Dong Yang, Ya Feng Yu * Pages 362-367
    Objective(s)

    We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice.

    Materials and Methods

    We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6–8 weeks and 42–44 weeks). Three groups of 42–44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry.

    Results

    Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42–44 weeks was lower compared with 6–8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group.

    Conclusion

    We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.

    Keywords: Auditory cortex, Mice, Mouse neurotrophic factor, Neuregulin-1, Presbycusis
  • Elham Hakimizadeh, Ayat Kaeidi, Zahra Taghipour, Saeed Mehrzadi, Mohammad Allahtavakoli, Ali Shamsizadeh, Gholamreza Bazmandegan, Jalal Hassanshahi, Mohammad Reza Aflatoonian, Iman Fatemi * Pages 368-375
    Objective(s)
    Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer’s disease. In the current investigation, the effect of Cef in a mice model of aging was investigated.
    Materials and Methods
    Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining.
    Results
    Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice.
    Conclusion
    Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.
    Keywords: Aging, Ceftriaxone, D-galactose, Mice, Oxidative stress
  • Tohid Naderi, Samira Mohammadi Yeganeh, Neda Mohammadi Hezaveh, Razie Hadavi, Ahmad Gharehbaghian, Nader Vazifeh Shiran, Vahid Fallah Azad, Mahdi Paryan * Pages 376-382
    Objective(s)

    microRNAs are small non-coding molecules that regulate gene expression in various biological processes. T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy accompanied with genetic aberrations and accounts for 20% of children’s and adult’s ALL. Notch signaling pathway dysregulation occurs in 60% of T-ALL cases. In the present study, we aimed to determine the relationship between miRNAs and genes involved in Notch signaling pathway.

    Materials and Methods

    Considering the role of the pathway and its down-stream genes in proliferation, differentiation, cell cycle, and apoptosis, NOTCH1, c-Myc, and CCND1 genes were selected as target genes. Using bioinformatics studies, miR-34a, miR-449a, miR-1827, and miR-106b were selected as miRNAs targeting the above-mentioned genes. We evaluated these genes and miRNAs in T-ALL clinical samples as well as Jurkat cell line, in which NOTCH1 is overexpressed.

    Results

    Quantitative Real-Time PCR indicated that NOTCH1, c-Myc, and CCND1 were overexpressed in samples with decreased expression of miR-34a. In addition, we observed that samples with decreased expression of miR-449a showed increased expression of NOTCH1 and CCND1. Furthermore, we analyzed the expression of miR-1827 and miR-106b, which target c-Myc and CCND1, respectively. We found out that the expression of miR-1827, miR-106b, and their respective target genes were inversely correlated in 80% and 75% of the cases (r=0.8), respectively. Furthermore, in Jurkat cell line, the expression of target genes was increased while the candidate miRNAs except miR-34a were decreased.

    Conclusion

    These miRNAs can be proposed as biomarkers and new therapeutic targets in T-ALL patients who have NOTCH1 overexpression.

    Keywords: Bioinformatics, Biomarker, miRNA, Notch signaling pathway, T-cell acute lymphoblastic leukemia
  • Shasha Wang, Meixing Yan, Yaoyao Guo, Runzhou Sun, Hong Jin, Yanling Gong * Pages 383-389
    Objective(s)
    Salsola collina is widely distributed along the Bohai coast and consumed as an edible plant by native residents. We have found surprisingly that S. collina extracts promoted gastrointestinal motility in mice previously. In the present study, effects of S. collina on gastrointestinal motility in rats and its underlying mechanism were explored.
    Materials and Methods
    In vivo, different fraction extracts from S. collina were prepared and the effects on gastric emptying and small intestinal propulsion in normal rats were measured. Plasma ghrelin (GRL), motilin (MTL), gastrin (GAS) and vasoactive intestinal peptide (VIP) and expressions of GRL receptor (GHSR), MTL receptor (MTLR), VIP receptor 2 (VIPR2) in the duodenum were also detected. In vitro, gastric antrum strips were prepared and activities of different extracts on gastric smooth muscle contractions were evaluated.
    Results
    Results showed that the ethyl acetate extract (EAE) was the most effective fraction to promote gastric emptying and intestinal propulsion, showing a dose-dependent manner. EAE increased plasma GRL and GAS, elevated GHSR expression and restrained VIPR2 expression in the duodenum. In vitro, EAE promoted contraction of normal gastric antrum strips as well as relaxed strips induced by atropine.
    Conclusion
    These data indicate that EAE has a significant prokinetic activity via a mechanism that mainly involves in modulating plasma GRL and GAS, expressions of GSHR and VIPR2 in the duodenum and activating M-cholinergic receptor. Our study provides a pharmacological basis for the use of S. collina extract in treating gastrointestinal motility disorders.
    Keywords: Atropine, epinephrine, Gastrointestinal Motility, Gastrointestinal hormones, Rat
  • Marjan Nassiri Asl, Ahmad Ghorbani, Sahar Salehisar, Elham Asadpour, Hamid Reza Sadeghnia * Pages 390-395
    Objective(s)

    Rutin is a flavonoid with potent antioxidant property, which exhibited cytoprotective effects in several models of neuronal injury. This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation (SGD) as an in vitro model of neurodegeneration and ischemia.

    Materials and Methods

    The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin or α-tocopherol (positive control) and then further incubated for 12 hr in SGD condition. Then, cell viability, DNA fragmentation, lipid peroxidation, generation of reactive oxygen species (ROS), and the expression of proteins involved in apoptosis were determined.

    Results

    The SGD condition significantly decreased viability of the cells, which was accompanied by a significant rise in the generation of ROS and lipid peroxidation. Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation. In addition, rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins (Bax, caspase-3, caspase-9) and increasing the level of anti-apoptotic protein Bcl-2.

    Conclusion

    This study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition. Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders.

    Keywords: Apoptosis, DNA, Oxidative stress, PC12, Rutin
  • Ritu Kulshrestha *, Apoorva Pandey, Amteshwar Jaggi, Surendra Bansal Pages 396-405
    Objective(s)
    The role of N-acetylcysteine (NAC) as an anti-oxidant in attenuating bleomycin-induced pulmonary fibrosis has been reported. However, its effect on parenchymal remodeling via regulating the protease-antiprotease balance is not fully defined. Therefore, the present study was designed to explore the possible role of matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP) and transforming growth factor-β1 (TGF-β1) pathway and their modulation by NAC in attenuating bleomycin-induced pulmonary fibrosis in rats.
    Materials and Methods
    Bleomycin sulphate (7 units/kg) was instilled inside the trachea to induce pulmonary fibrosis. The time course of TGF-β1, MMP-9, TIMP-1,3 mRNA and protein expression, TGF-β1 and hydroxyproline levels were evaluated on days 7, 14, and 28. NAC (0.3 mmol/kg and 3 mmol/kg) was administered in bleomycin-instilled animals.
    Results
    NAC treatment significantly attenuated bleomycin-induced histopathological changes by decreasing interstitial inflammation and reducing the deposition of extracellular matrix proteins such as collagen. Moreover, it increased the mRNA and protein expression of MMP-9 and decreased the expression of TIMP-1,3 in alveolar epithelial cells (AECs), interstitial macrophages and inflammatory cells. Indeed, there was decrease in the MMP-9/TIMP ratio in bleomycin-instilled rats, which increased with NAC treatment. Moreover, NAC attenuated bleomycin-induced increased expression of TGF-β1 and total lung collagen levels.
    Conclusion
    NAC attenuates bleomycin-induced pulmonary fibrosis by normalizing the protease-antiprotease balance and favoring the degradation of collegen to reduce fibrosis.
    Keywords: Bleomycin, MMP-9, N-acetylcysteine, Pulmonary Fibrosis, TGF-β1, TIMPs