Antipsychotic-induced oxidative stress in rat brain.
Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D(2) dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic (28 days) HAL, clozapine (CLO), olanzapine (OLZ) or aripiprazole (ARI) administration. Adult male Wistar rats received daily injections of HAL (1.5 mg/kg), CLO (25 mg/kg), OLZ (2.5, 5 or 10 mg/kg) or ARI (2, 10 or 20 mg/kg); control animals received vehicle (Tween 1% solution). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the prefrontal cortex, hippocampus, striatum and cerebral cortex. The results showed that TBARS were increased in the striatum after HAL treatment. On the other hand, TBARS were diminished in the prefrontal cortex by OLZ and ARI. Our results also showed that all drugs tested in this work decreased TBARS levels in the cerebral cortex. In hippocampus, TBARS levels were not altered by any drug. Protein carbonyl content after HAL and CLO treatment was increased in the hippocampus. Moreover, OLZ and ARI did not alter protein carbonyl content when compared to control group. ARI chronic administration (20 mg/kg) also increased mitochondrial superoxide in the prefrontal cortex and striatum. ARI did not alter mitochondrial superoxide in the hippocampus and cerebral cortex. Moreover, HAL, OLZ and CLO did not cause significant alterations in mitochondrial superoxide in rat brain. Our findings demonstrate that OLZ and ARI do not induce oxidative damage in rat brain as observed after HAL and CLO treatment.
Martins
Márcio R
MR
Laboratório de Neurociencias, Programa de Pós-graduacao em Cicecias da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Petronilho
Fabrícia C
FC
Gomes
Karin M
KM
Dal-Pizzol
Felipe
F
Streck
Emilio L
EL
Quevedo
João
J
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000633:toxicity; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003024:Clozapine / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000077152:Olanzapine; D018384:Oxidative Stress / Q000187:drug effects*; D010879:Piperazines / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D001569:Benzodiazepines; D000068180:Aripiprazole; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine