Haloperidol- and clozapine-induced oxidative stress in the rat brain.
Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D2 dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg) or clozapine (CLO, 25 mg/kg), an atypical neuroleptic, for 28 days. Control animals were given saline (SAL; NaCl 0.9%). Oxidative parameters in the brain were measured in the striatum (ST), hippocampus (HP) and cortex (CX). Thiobarbituric acid (TBA) reactive substances (TBAR) levels were increased by HAL treatment in the ST and decreased in CX of both of the HAL- and CLO-treated rats. Protein carbonyls were significantly increased by both HAL and CLO in the HP. The nonenzymatic antioxidant potential was decreased in the HP, and superoxide production was significantly increased in the ST following treatment with HAL. CLO induced an increase in superoxide production in the HP. Neither HAL nor CLO affected catalase (CAT) and superoxide dismutase (SOD) activities. The findings suggest that HAL and CLO can induce oxidative damage to the ST and HP in rats.
Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
Manuela
M
Polydoro
Nadja
N
Schröder
Maria Noemia M
MN
Lima
Fábio
F
Caldana
Daniela C
DC
Laranja
Elke
E
Bromberg
Rafael
R
Roesler
João
J
Quevedo
José Cláudio F
JC
Moreira
Felipe
F
Dal-Pizzol
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D014150:Antipsychotic Agents; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D003024:Clozapine; D006220:Haloperidol