Olanzapine protects PC12 cells from oxidative stress induced by hydrogen peroxide

Abstract

Neuroanatomical studies suggest that neuronal atrophy and destruction occur over the course of many years in neurodegenerative conditions such as schizophrenia and Alzheimer's disease. In schizophrenia, early intervention with atypical neuroleptics such as olanzapine has been shown to prevent development of some of the more serious and debilitating symptoms in many patients. The mechanisms whereby olanzapine slows or prevents symptom progression in schizophrenia remain unclear. A previous study found that olanzapine increased mRNA for the copper/zinc isoform of the superoxide dismutase enzyme (SOD-1). We investigated the effects of olanzapine in PC12 cells exposed to hydrogen peroxide. We measured cell viability, observed evidence of necrosis and apoptosis, checked the SOD-1 mRNA by Northern blot analyses, and determined SOD-1 enzyme activity. We found that: (1) the decrease in cell viability induced by hydrogen peroxide was attenuated in PC12 cells pretreated with olanzapine; (2) olanzapine increased SOD enzyme activity in PC12 cells; (3) inhibiting SOD activity with diethyldithiocarbamic acid prevented the cytoprotective actions of olanzapine; and (4) the decrease in SOD-1 mRNA level induced by hydrogen peroxide was blocked by pretreatment with olanzapine. These data indicate that the neuroprotective action of olanzapine includes the upregulation of SOD.

Olanzapine Attenuates the Okadaic Acid-Induced Spatial Memory Impairment and Hippocampal Cell Death in Rats

“…In PC12 cells, olanzapine is effective in reducing the cell death induced by H 2 O 2 , Ab, or MPP þ , which may cause oxidative stress thus killing the treated cells (Qing et al, 2003;Wei et al, 2003a, b). We demonstrated that these cytoprotective actions in the cells might involve the upregulation of superoxide dismutase-1, one of the endogenous antioxidant enzymes, by the drug (Li et al, 1999;Qing et al, 2003;Wei et al, 2003a). In addition, olanzapine can regulate the translocation and expression of pro-and antiapoptotic proteins Bax and Bcl-X L in PC12 cells (Wei et al, 2003b).…”

Effect of Chronic Exposure to Antipsychotic Medication on Cell Numbers in the Parietal Cortex of Macaque Monkeys

“…Conversely, olanzapine promotes the activation of antiapoptotic pathways in rodent frontal cortex (Bai et al, 2004;Fumagalli et al, 2006;Wang et al, 2001) and in pheochromocytoma cells (Lu et al, 2004). In addition, olanzapine also protects pheochromocytoma cells from cytotoxic oxidative damage (Wei et al, 2003). Thus, antipsychotic-induced cell death is not a parsimonious explanation for lower glial cell number and higher neuron density in both the haloperidol and olanzapine groups.…”

Oxidative stress in psychiatric disorders: evidence base and therapeutic implications

“…Olanzapine (Wei et al, 2003) ; clozapine, olanzapine, quetiapine, risperidone Antioxidant therapies Trial design Treatment outcomes Sample size (n)…”

“…Haloperidol-induced oxidative stress parameters in rats have also been shown to be ameliorated by the antioxidant drug, Nacetylcysteine (NAC) (Harvey et al, 2007). In-vitro cell studies have demonstrated a protective effect of atypicals, such as olanzapine and quetiapine, on PC12 cells exposed to oxidative stress Wei et al, 2003).…”