title: Neuroprotective effect of noscapine on cerebral oxygen-glucose deprivation injury.
abstract: BACKGROUND
  The present study aims to investigate the effect of noscapine (0.5-2.5 μM), an alkaloid from the opium poppy, on primary murine fetal cortical neurons exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia.
  
  
  METHODS
  Cells were transferred to glucose-free DMEM and were exposed to hypoxia in a small anaerobic chamber. Cell viability and nitric oxide production were evaluated by MTT assay and the Griess method, respectively.
  
  
  RESULTS
  The neurotoxicities produced by all three hypoxia durations tested were significantly inhibited by 0.5 μM noscapine. Increasing noscapine concentration up to 2.5 μM produced a concentration-dependent inhibition of neurotoxicity. Pretreatment of cells with MK-801 (10 μM), a non-competitive NMDA antagonist, and nimodipine (10nM), an L-type Ca(2+) channel blockers, increased cell viability after 30 min OGD, while the application of NBQX (30 μM), a selective AMPA-kainate receptor antagonist partially attenuated cell injury. Subsequently, cells treated with noscapine in the presence of thapsigargin (1 μM), an inhibitor of endoplasmic reticulum Ca(2+) ATPases. After 60 min OGD, noscapine could inhibit the cell damage induced by thapsigargin. However, noscapine could not reduce cell damage induced by 240 min OGD in the presence of thapsigargin. Noscapine attenuated nitric oxide (NO) production in cortical neurons after 30 min OGD.
  
  
  CONCLUSIONS
  We concluded that noscapine had a neuroprotective effect, which could be due to its interference with multiple targets in the excitotoxicity process. These effects could be mediated partially by a decrease in NO production and the modulation of intracellular calcium levels.
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Vahabzadeh.g@iums.ac.ir.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Vahabzadeh
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Rahbar-Roshandel
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Soltan-Ahmad
authors.initials: SA
authors.lastname: Ebrahimi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Mahmoudian
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency*; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009553:Nimodipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009665:Noscapine / Q000494:pharmacology* / Q000627:therapeutic use; D061251:Primary Cell Culture; D011810:Quinoxalines / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D009569:Nitric Oxide; D009553:Nimodipine; D019284:Thapsigargin; D016291:Dizocilpine Maleate; D009665:Noscapine; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester
keywords: Cortical culture; NO; Noscapine; Oxygen–glucose deprivation