title: Effects of haloperidol and clozapine administration on oxidative stress in rat brain, liver and serum.
abstract: Antipsychotics remain the standard of care for individuals with schizophrenia, despite their association with adverse effects including extrapyramidal symptoms, metabolic syndrome and agranulocytosis. While the biological mechanisms underlying these side effects remain unresolved, it has been proposed that oxidative stress may play a role in their development. The aim of this study was to evaluate markers of oxidative stress associated with first- and second-generation antipsychotics, focusing on protein and lipid oxidation and expression of the antioxidant proteins peroxiredoxin-2 and peroxiredoxin-6. Following 28-day administration of haloperidol, clozapine or saline to adult rats, brain grey matter, white matter, serum and liver samples were obtained and lipid peroxidation, protein oxidation, peroxiredoxin-2 and peroxiredoxin-6 levels quantified. In grey matter, peroxiredoxin-6 was significantly increased in the haloperidol-exposed animals, with a trend towards increased lipid peroxidation also observed in this group. In liver, lipid peroxidation was increased in the clozapine-exposed animals, with a similar trend noted in the haloperidol group. Antipsychotics did not produce significant changes in serum or white matter. Our results suggest that haloperidol and clozapine may induce oxidative stress in brain and liver, respectively, consistent with the documented adverse effects of these agents.
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Ana C
authors: AC
authors: Andreazza
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Vilte E
authors: VE
authors: Barakauskas
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Salar
authors: S
authors: Fazeli
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Abigail
authors: A
authors: Feresten
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Li
authors: L
authors: Shao
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Vivien
authors: V
authors: Wei
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors: Che Hsuan
authors: CH
authors: Wu
authors: Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors: Alasdair M
authors: AM
authors: Barr
authors: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada. Electronic address: cbeasley@mail.ubc.ca.
authors: Clare L
authors: CL
authors: Beasley
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D054464:Peroxiredoxins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044967:Serum
chemical_list: D014150:Antipsychotic Agents; D054464:Peroxiredoxins; D003024:Clozapine; D006220:Haloperidol
keywords: Antioxidant; Antipsychotic agent; Lipid peroxidation; Peroxiredoxin; Schizophrenia