title: Neuroprotection of paliperidone on SH-SY5Y cells against β-amyloid peptide(25-35), N-methyl-4-phenylpyridinium ion, and hydrogen peroxide-induced cell death.
abstract: BACKGROUND
  Antipsychotic drugs (APDs) were widely used in treating schizophrenia. Some APDs were reported to have neuroprotective effects against neurotoxicants in the cell level.
  
  
  OBJECTIVE
  Thus, one typical APD (haloperidol) and three atypical APDs (paliperidone, olanzapine, and risperidone) were tested whether they provide neuroprotection against stressor-induced cell death of SH-SY5Y.
  
  
  METHODS
  Hydrogen peroxide, N-methyl-4-phenylpyridinium ion, and β-amyloid peptide were used to treat cells with or without preconditioning by APDs; cell survival and indicators of oxidative stress were measured, respectively.
  
  
  RESULTS
  Paliperidone has the lowest baseline cytotoxicity compared with other APDs at 24 h; in addition, the paliperidone group showed a better survival than the other APD groups (P < 0.05). In stressor challenging, with a fixed concentration of stressors, olanzapine provided the best neuroprotection at 100 μM against Aβ(25-35) and MPP(+) (P < 0.05). In contrast, paliperidone works finely at low concentrations (10 and 50 μM) against Aβ(25-35) and MPP(+) and solely protected SH-SY5Y from hydrogen peroxide. At 100 μM, paliperidone completely diminished cell reduction induced by different stressors, regardless of their dosages. Paliperidone was demonstrated with a higher oxidative stress-scavenging properties than other APDs in several aspects, such as generated bulk glutathione, low HNE, and protein carbonyl productions. Contradictorily, olanzapine, at 24 h, also enhanced HNE and protein carbonyl productions, which may underlie its induced cytotoxicity.
  
  
  CONCLUSIONS
  Different APDs exhibit variations against different stressors. Paliperidone might be useful not only in alleviating oxidative stress induced by Aβ(25-35) and MPP(+) but also in providing neuroprotection against hydrogen peroxide.
authors.affiliation: Center for Genetic Laboratory, Kaohsiung, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Yang
authors.forename: For-Wey
authors.initials: FW
authors.lastname: Lung
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007555:Isoxazoles / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D000068882:Paliperidone Palmitate; D010446:Peptide Fragments / Q000633:toxicity*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D007555:Isoxazoles; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011743:Pyrimidines; C074636:amyloid beta-protein (25-35); D006861:Hydrogen Peroxide; D015655:1-Methyl-4-phenylpyridinium; D000068882:Paliperidone Palmitate