title: Mangiferin ameliorates 6-hydroxydopamine-induced cytotoxicity and oxidative stress in ketamine model of schizophrenia.
abstract: BACKGROUND
  Accumulating evidence indicates that mangiferin (MGF), a natural xanthone, by virtue of its antioxidant and antiinflammatory properties is neuroprotective. Here we sought to verify the cytoprotective role of MGF on cultured rat primary mesencephalic cells exposed to 6-hydroxydopamine (6-OHDA) in vitro, and the MGFs anti-inflammatory potential in mouse model of ketamine-induced schizophrenia in vivo.
  
  
  METHODS
  3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay was performed tomeasure cell viability inmesencephalic cell cultures exposed to neurotoxin (6-OHDA, 40 μM). Schizophrenia was induced in mice by ketamine (50 mg/kg, ip, twice a day, for 7 days). The treatment effects of MGF (50 mg/kg, po, for 7 days) were verified on locomotor behavioral changes in open-field test, and on the oxidant stress-related increase in lipid-peroxidation (malondialdehyde) and interleukin-6 (IL-6) levels in brain tissues.
  
  
  RESULTS
  MGF (10-100 μM) produced no per se effect on cell viability as measured by MTT assay, but significantly prevented the 6-OHDA-induced cell death in a concentration-dependent manner. Acridine orange/ethidium bromide (AO/EtBr) staining confirmed the absence of 6-OHDA-induced morphological changes characteristic of apoptosis/necrosis. In open-field test, ketamine-induced impaired locomotor activity and behavioral changes such as grooming and stereotyped but not rearing were effectively ameliorated by MGF pretreatment. Also, ketamine-associated increase in brain tissue levels of IL-6 and MDA were significantly lowered in MGF-pretreated mice.
  
  
  CONCLUSIONS
  Mangiferin has a neurocytoprotective role related, at least in part, to an antioxidant and anti-inflammatory mechanism, which could be explored for more effective therapies of schizophrenia and other neurodegenerative diseases.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil. vietrao@ufc.br
authors.forename: Vietla S
authors.initials: VS
authors.lastname: Rao
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Maria Teresa S
authors.initials: MT
authors.lastname: Trevisan
authors.forename: Geanne M
authors.initials: GM
authors.lastname: Andrade
authors.forename: Helio V
authors.initials: HV
authors.lastname: Nobre-Júnior
authors.forename: Manoel O
authors.initials: MO
authors.lastname: Moraes
authors.forename: Hemerson I
authors.initials: HI
authors.lastname: Magalhães
authors.forename: Talita C
authors.initials: TC
authors.lastname: Morais
authors.forename: Flavia A
authors.initials: FA
authors.lastname: Santos
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000009:adverse effects*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015850:Interleukin-6; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009573:Nitrites; D044004:Xanthones; C013592:mangiferin; D008315:Malondialdehyde; D007649:Ketamine; D016627:Oxidopamine