Neuroprotection of paliperidone on SH-SY5Y cells against β-amyloid peptide(25-35), N-methyl-4-phenylpyridinium ion, and hydrogen peroxide-induced cell death

Rationale: Antipsychotic drugs (APDs) were widely used in treating schizophrenia. Some APDs were reported to have neuroprotective effects against neurotoxicants in the cell level.

Objectives: 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.