Protective effects of atypical antipsychotic drugs against MPP+-induced oxidative stress in PC12 cells

▶ Some atypical antipsychotic drugs have protective effects against oxidative stress. ▶ We observe antioxidant effect using MPP+ toxicity model causing oxidative stress. ▶ Olanzapine, aripiprazole and ziprasidone modulate the levels of ROS, SOD and Bax. ▶ However, haloperidol fails to show antioxidant effects. ▶ These atypical antipsychotic drugs have antioxidant effects with clinical relevance. 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.