Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide.
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.
Kolla
Nathan
N
Neuropsychiatry Research Unit, Department of Psychiatry, University of Saskatchewan.
Wei
Zelan
Z
Richardson
J Steven
JS
Li
Xin-Min
XM
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
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D016877:Oxidants; D005473:Fluoxetine; D000639:Amitriptyline; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase