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Olanzapine and quetiapine protect PC12 cells from β‐amyloid peptide 25–35 ‐induced oxidative stress and the ensuing apoptosis
Author(s) -
Wang Haitao,
Xu Haiyun,
Dyck Lillian E.,
Li XinMin
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20570
Subject(s) - oxidative stress , quetiapine , olanzapine , pharmacology , superoxide dismutase , chemistry , reactive oxygen species , glutathione peroxidase , atypical antipsychotic , biology , medicine , biochemistry , antipsychotic , schizophrenia (object oriented programming) , psychiatry
We previously found that the atypical antipsychotic drugs (APDs) clozapine, olanzapine, quetiapine, and risperidone reduce PC12 cell death induced by hydrogen peroxide, N‐methyl‐4‐phenylpyridinium ion, or β‐amyloid peptide (Aβ 25–35 ). Such neurotoxic substances have in common the capability of causing oxidative stress. Atypical APDs have been used in treating schizophrenia and in treating psychotic symptoms of patients with Alzheimer's disease (AD), in which Aβ is involved by causing oxidative stress. Therefore, we hypothesized that atypical APDs might alleviate oxidative stress in PC12 cells, thus protecting them from apoptosis. PC12 cells were seeded in plates or chambers for 24 hr and cultured for another 24 hr with olanzapine or quetiapine in the medium, and then the cells were cultured in the new medium containing Aβ 25–35 and/or olanzapine, quetiapine, but not serum, for various periods. It was shown that cultures treated with olanzapine + Aβ 25–35 , or quetiapine + Aβ 25–35 , had significantly higher cell viabilities and lower rates of apoptosis compared with the cultures exposed only to Aβ 25–35 . In addition, the drugs blocked the activation of caspase‐3 caused by Aβ 25–35 . Furthermore, olanzapine and quetiapine prevented Aβ 25–35 ‐induced overproduction of intracellular reactive oxygen species, Aβ 25–35 ‐induced decrease in mitochondrial membrane potential, and Aβ 25–35 ‐induced changes in activities of the key antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. In consideration of the wealth of evidence linking oxidative stress to the pathophysiology of schizophrenia and AD, these findings give us a new insight into the therapeutic actions of atypical antipsychotics in patients with the disorders. © 2005 Wiley‐Liss, Inc.