title: Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide.
abstract: OBJECTIVE
  To investigate the potential protective effects of amitriptyline and fluoxetine in a catecholamine cell model.
  
  
  METHODS
  Cultured rat pheochromocytoma (PC12) cells were pretreated with amitriptyline or fluoxetine for 24 or 48 hours and were then subjected to neurotoxic insult (200 micromol/L hydrogen peroxide). Cell viability was determined by measurement of the reduction product of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The enzyme activity of superoxide dismutase (SOD) was determined by a commercial SOD assay kit.
  
  
  RESULTS
  The decrease in cell viability induced by hydrogen peroxide was attenuated in PC12 cells pretreated with 100 micromol/L amitriptyline for 24 hours or with 50 micromol/L amitriptyline or 50 micromol/L fluoxetine for 48 hours. Pretreatment with either amitriptyline or fluoxetine was associated with increased SOD activity in PC12 cells. Inhibition of SOD activity with diethyldithiocarbamic acid reduced the cytoprotective action of fluoxetine.
  
  
  CONCLUSIONS
  These data suggest that the neuroprotective actions of some antidepressants include the upregulation of SOD activity.
authors.affiliation: Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan.
authors.forename: Nathan
authors.initials: N
authors.lastname: Kolla
authors.forename: Zelan
authors.initials: Z
authors.lastname: Wei
authors.forename: J Steven
authors.initials: JS
authors.lastname: Richardson
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000975:Antioxidants; D002470:Cell Survival / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D016877:Oxidants; D005473:Fluoxetine; D000639:Amitriptyline; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase