Effect of atypical antipsychotics on antioxidant enzyme activities in human erythrocytes (in vitro study)

Hum Psychopharmacol. 2013 Jan;28(1):1-6. doi: 10.1002/hup.2272. Epub 2012 Nov 5.

Abstract

Objective: This study was set out to examine the impact of atypical antipsychotic drugs: aripiprazole, clozapine, ziprasidone, olanzapine, quetiapine, sertindole and amisulpride on the activity of antioxidant defence enzymes in human erythrocytes in vitro.

Methods: Cu,Zn-superoxide dismutase (SOD1), catalase (CAT), selenium-dependent glutathione peroxidase and glutathione reductase activities were determined after drugs incubation with blood of 15 apparently healthy non-smoking male volunteers (ages 23-39) for 1 h at 37 °C.

Results: A statistically significant increase in SOD1 activity was found in samples incubated with aripiprazole (p < 0.01) and quetiapine (p < 0.05) compared with incubated control. SOD1 activity profile following native polyacrylamide gel electrophoresis indicates that aripiprazole and quetiapine protect enzyme activity from inhibition with hydrogen peroxide. Our results showed that sertindole decreases activity of CAT comparing with control non-treated erythrocytes. Moreover, in sertindole treated erythrocytes, negative correlation between SOD1 and glutathione peroxidase activities was found. Increased amount of hydrogen peroxide in such situation may leave erythrocytes and transform their role in circulation from anti-oxidative to pro-oxidative.

Conclusions: Our results indicate that mechanism through sertindole could express its in vivo toxic effects and point toward possible (neuro)protective effects of aripiprazole and quetiapine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amisulpride
  • Antioxidants / metabolism*
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole
  • Benzodiazepines / metabolism
  • Catalase / metabolism
  • Clozapine / metabolism
  • Dibenzothiazepines / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Erythrocytes / drug effects*
  • Erythrocytes / enzymology*
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Humans
  • Imidazoles / metabolism
  • Indoles / metabolism
  • Male
  • Olanzapine
  • Piperazines / metabolism
  • Quetiapine Fumarate
  • Quinolones / metabolism
  • Sulpiride / analogs & derivatives
  • Sulpiride / metabolism
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Thiazoles / metabolism
  • Treatment Outcome
  • Young Adult

Substances

  • Antioxidants
  • Antipsychotic Agents
  • Dibenzothiazepines
  • Imidazoles
  • Indoles
  • Piperazines
  • Quinolones
  • SOD1 protein, human
  • Thiazoles
  • Benzodiazepines
  • Quetiapine Fumarate
  • ziprasidone
  • Sulpiride
  • Amisulpride
  • Aripiprazole
  • Catalase
  • Glutathione Peroxidase
  • selenium-independent glutathione peroxidase
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Glutathione Reductase
  • sertindole
  • Clozapine
  • Olanzapine