2009
DOI: 10.1016/j.brainres.2009.05.063
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Clozapine protects PC-12 cells from death due to oxidative stress induced by hydrogen peroxide via a cell-type specific mechanism involving inhibition of extracellular signal-regulated kinase phosphorylation

Abstract: Recent evidence suggests that some atypical antipsychotic drugs may protect against oxidative stress and consequent neurodegeneration by mechanisms that remain unclear. Using the neuron-like rat pheochromocytoma (PC-12) cell line, Clozapine and N-desmethylclozapine were tested for their ability to protect against cell death due to oxidative stress induced by hydrogen peroxide (H 2 O 2 ). These drugs demonstrated significant protection of PC-12 cells, as measured by both the 3-(4,5-dimethylthiazol-2-yl)-2,5-dip… Show more

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Cited by 54 publications
(22 citation statements)
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“…Clozapine blocks neurotoxicity in the rat cortex induced by noncompetitive NMDA receptor antagonist dizocilpine [16]. It may also provide some degree of neuroprotection, specifically against oxidative stress [17]. Using an animal model, Moller et al [18] showed that clozapine may reverse cortico-striatal oxidative stress.…”
Section: Introductionmentioning
confidence: 99%
“…Clozapine blocks neurotoxicity in the rat cortex induced by noncompetitive NMDA receptor antagonist dizocilpine [16]. It may also provide some degree of neuroprotection, specifically against oxidative stress [17]. Using an animal model, Moller et al [18] showed that clozapine may reverse cortico-striatal oxidative stress.…”
Section: Introductionmentioning
confidence: 99%
“…Haloperidol and quetiapine have demonstrated a significantly reduced expression of genes encoded for antioxidant enzymes (e.g., glutathione-Stransferase), which may underlie the molecular mechanism of their cytotoxicity (Schmidt et al 2009). Clozapine did not have a neuroprotective effect against hydrogen peroxide on SH-SY5Y, but had a protective effect toward PC12 (Magliaro and Saldanha 2009) under hydrogen peroxide treatment. Similarly, olanzapine, an APD very close to clozapine, was also observed to have a protective effect on PC12 against hydrogen peroxide (Wei et al 2003a).…”
Section: Discussionmentioning
confidence: 79%
“…Moreover, atypical APDs modulated Bax and Bcl-XL/S expression and localization (Wei et al 2003b). Enhanced phosphorylation of the ERK signaling pathway by clozapine against hydrogen peroxide in PC12 also indicated that other molecular events outside of attenuating free radicals may contribute to the neuroprotection of clozapine (Magliaro and Saldanha 2009). Taken together, different APDs exhibited different therapeutic effects via regulating convergent or distinct signaling pathways.…”
Section: Discussionmentioning
confidence: 88%
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“…5) PC12 cells with neuron-like characteristics in vitro constitute a widely used neuronal model system to study cellular hydrogen peroxide (H 2 O 2 ) toxicity. [6][7][8] Therefore, H 2 O 2 was used as an exogenous lesion to elucidate the protective action of ginkgolide K in H 2 O 2 -induced PC12 cells in vitro.…”
mentioning
confidence: 99%