title: Generalized estimating equation model and long-term exposure effect of antipsychotics on SH-SY5Y cells against oxidative stressors.
abstract: A comparison of the neuroprotective effect of different antipsychotics (APDs) over time on naïve SH-SY5Y against oxidative stressor insults using the generalized estimating equation (GEE). The hydrogen peroxide (H2O2), N-methyl-4-phenylpyridinium ion (MPP+), and β-amyloid peptide were used to treat cells with or without APDs (paliperidone, risperidone, olanzapine and haloperidol); cell survival and oxidative stress markers were measured and analyzed. Only haloperidol had higher baseline cytotoxicity than paliperidone. GEE showed the proper exposure time for evaluating the neuroprotection of APDs was 24 h, rather than 48 or 72 h. Paliperidone was superior to other APDs in protecting naïve SH-SY5Y, had the best effect against H2O2-, MPP+-induced cell death, and caused a significantly higher GST, lower HNE and protein carbonyl productions of naïve SH-SY5Y after stressor insults, which may implicate a molecular mechanism underlying its neuroprotective action. Repeated GEE measurements can correct for the correlation among the clusters to obtain a more accurate result for evaluating drug outcome. The interaction between drugs and stressors should be taken into account when determining the neuroprotective effect of APDs against different stressors. Paliperidone might be useful in alleviating oxidative stress induced by Aβ25-35 and MPP+, and provide neuroprotection against hydrogen peroxide in naïve SH-SY5Y.
authors: Department of Psychiatry, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan, ROC; Institute of Biological Science, National Sun Yat-sen University, Kaohsiung City, Taiwan, ROC.
authors: Ming-Chang
authors: MC
authors: Yang
authors: Taipei City Hospital, Songde Branch, Taipei, Taiwan, ROC.
authors: Kun-Po
authors: KP
authors: Chen
authors: Taipei City Hospital, Songde Branch, Taipei, Taiwan, ROC; Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: forwey@seed.net.tw.
authors: For-Wey
authors: FW
authors: Lung
mesh_terms: D015655:1-Methyl-4-phenylpyridinium; D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077152:Olanzapine; D018384:Oxidative Stress / Q000187:drug effects; D000068882:Paliperidone Palmitate / Q000494:pharmacology; D010446:Peptide Fragments; D050050:Protein Carbonylation / Q000187:drug effects; D018967:Risperidone / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D001569:Benzodiazepines; D006861:Hydrogen Peroxide; D005978:Glutathione; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine; D015655:1-Methyl-4-phenylpyridinium; D000068882:Paliperidone Palmitate
keywords: Antipsychotics; Atypical antipsychotics; Generalized estimating equation; Hydrogen peroxide; Neuroprotection; β-amyloid