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. 2005 May;30(3):196-201.

Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide

Nathan Kolla  1 , Zelan Wei, J Steven Richardson, Xin-Min Li
Affiliations

Amitriptyline and fluoxetine protect PC12 cells from cell death induced by hydrogen peroxide

Nathan Kolla et al. J Psychiatry Neurosci. 2005 May.

Abstract
in English, French

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.

Objectif: Étudier les effets protecteurs possibles de l'amitriptyline et de la fluoxétine dans un modèle cellulaire de catécholamines.

Méthodes: On a appliqué à des cellules cultivées de phéochromocytome (PC12) de rat un prétraitement de 24 ou de 48 heures à l'amitriptyline ou à la fluoxétine, puis on a induit une atteinte neurotoxique (200 μmol/L de peroxyde d'hydrogène). La viabilité des cellules a été établie par la mesure du produit de réduction du bromure de 3-[4,5-diméthylthiazol-2-yl]-2,5-diphényl-tétrazolium (MTT). L'activité enzymatique de la superoxide dismutase (SOD) a été établie au moyen d'une trousse du commerce pour le dosage de la SOD.

Résultats: Le prétraitement des cellules de PC12 au moyen de 100 μmol/L d'amitriptyline pendant 24 heures ou de 50 μmol/L d'amitriptyline ou de fluoxétine pendant 48 heures a atténué la diminution de la viabilité des cellules causée par le peroxyde d'hydrogène. Le prétraitement aussi bien à l'amitriptyline qu'à la fluoxétine a été associé avec une augmentation de l'activité enzymatique de la SOD dans les cellules de PC12. L'inhibition de l'activité de la SOD au moyen de l'acide diéthyldithiocarbamique a réduit l'action de cytoprotection de la fluoxétine.

Conclusions: Ces données semblent indiquer que l'action de neuroprotection de certains antidépresseurs comprend une régulation à la hausse de l'activité de la SOD.

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Figures

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Fig. 1: Effects of antidepressants on 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction and superoxide dismutase (SOD) activity of PC12 cells. Cells were treated with amitriptyline (AMI) or fluoxetine (FLU) for 24 hours (A, C) or 48 hours (B, D). MTT reduction assay (A, B) and test for SOD activity (C, D) were carried out according to the Methods. Data are presented as mean (and standard error of the mean), from 4 independent experiments for the MTT assay and 3 independent experiments for SOD activity.
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Figure 1. Continued.
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Fig. 2: Effects of antidepressants and diethyldithiocarbamic acid (DETC) on hydrogen peroxide-induced neurotoxicity in PC12 cells. Before being exposed to 200 μmol/L H2O2 for 4 hours, cells were pretreated with (A) 100 μmol/L amitriptyline (AMI) or 100 μmol/L fluoxetine (FLU) for 24 hours; (B) 50 μmol/L amitriptyline or 50 μmol/L fluoxetine for 48 hours; or (C) 50 μmol/L fluoxetine or 50 μmol/L fluoxetine plus 1.0 mmol/L DETC (D) for 48 hours. Data are presented as mean (and standard error of the mean) from 4 independent experiments. *p < 0.001 v. vehicle control (VEH); †p < 0.01 v. 200 μmol/L H2O2 treatment alone; ‡p < 0.001 v. 200 μmol/L H2O2 treatment alone.
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Figure 2. Continued.
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Figure 2. Continued.
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Fig. 3: Effects of antidepressants and diethyldithiocarbamic acid (DETC) on superoxide dismutase (SOD) activity of PC12 cells. PC12 cells were treated with (A) vehicle (VEH), 200 μmol/L hydrogen peroxide for 4 hours, 100 μmol/L amitriptyline (AMI) for 24 hours or 100 μmol/L fluoxetine (FLU) for 24 hours; (B) vehicle, 200 μmol/L H2O2 for 4 hours, 50 μmol/L amitriptyline for 48 hours or 50 μmol/L fluoxetine for 48 hours; (C) vehicle, 50 μmol/L fluoxetine for 48 hours, 1.0 mmol/L DETC for 48 hours, or 50 μmol/L fluoxetine plus 1.0 mmol/L DETC for 48 hours. Data are presented as mean (and standard error of the mean) from 4 independent experiments. *p < 0.05 v. vehicle control.
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Figure 3. Continued.
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Figure 3. Continued.
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