Protective effects of atypical antipsychotic drugs against MPP(+)-induced oxidative stress in PC12 cells.
Recent studies have suggested that some atypical antipsychotic drugs may have protective properties against oxidative stress. To confirm these findings, we investigated the protective effects of atypical antipsychotic drugs such as olanzapine, aripiprazole, and ziprasidone on oxidative stress induced by the N-methyl-4-phenylpyridinium (MPP(+)) ion in PC12 cells. Haloperidol, a typical antipsychotic drug, was used for comparison. We determined the antioxidant effects of atypical antipsychotic drugs using a number of measures, including cell viability, the formation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and Bax levels. MPP(+) treatment induced significant loss of cell viability, the formation of ROS, reduction of SOD activity, and up-regulation of Bax expression. However, olanzapine, aripiprazole and ziprasidone reversed these effects caused by MPP(+) treatment, but ziprasidone did not influence cell viability. In contrast, haloperidol did not affect all these effects. Moreover, haloperidol strongly increased the expression of Bax under MPP(+)-free conditions. Olanzapine, aripiprazole, and ziprasidone, but not haloperidol, may exert antioxidant effects through modulating ROS levels, SOD activity, and Bax expression to provide protective effects against MPP(+)-induced oxidative stress in PC12 cells. These results suggest that some atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress in schizophrenic patients.
Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
Sung Woo
SW
Park
Chan Hong
CH
Lee
Jung Goo
JG
Lee
Luck Woo
LW
Kim
Bae Sub
BS
Shin
Bong Ju
BJ
Lee
Young Hoon
YH
Kim
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006540:Herbicides / Q000633:toxicity; D000077152:Olanzapine; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D014150:Antipsychotic Agents; D006540:Herbicides; D010879:Piperazines; D015363:Quinolones; D017382:Reactive Oxygen Species; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D001569:Benzodiazepines; C092292:ziprasidone; D000068180:Aripiprazole; D013482:Superoxide Dismutase; D006220:Haloperidol; D000077152:Olanzapine; D015655:1-Methyl-4-phenylpyridinium