title: Sulforaphane protects SK-N-SH cells against antipsychotic-induced oxidative stress.
abstract: Adverse reactions to antipsychotic drugs (APs) have been attributed to oxidative stress. Sulforaphane (SF) is a potent antioxidant that protects against dopaminergic cell death. We examined the protective properties of SF against AP-induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK-N-SH cells were treated with SF (0.5-5 μM), and 24 h later, haloperidol, risperidone or paliperidone (100 μM) was administered, either alone or in combination with dopamine (100 μM). To determine the antioxidant properties of SF, quinone oxidoreductase (NQO1) activity, glutathione S-transferase activity, and glutathione (GSH) levels were determined. Oxidative stress was measured by the increase in thiobarbituric acid reactive substances (TBARS) and in protein-bound quinones. Cell viability was also assessed. SF treatment increased GSH levels and induced NQO1 activity in SK-N-SH cells. Haloperidol was the only AP that increased TBARS when administered alone. When cells were cocultured with a drug in combination with dopamine, all three APs increased TBARS and protein-bound quinones and also induced neurotoxicity. In all the experimental conditions, 5 μM SF attenuated the accumulation of TBARS and protein-bound quinones and increased cell survival rates. Our results indicate that SF increases GSH levels and induces NQO1 activity and the removal of electrophilic quinones and radical oxygen species. Furthermore, SF could provide protective effects against AP-induced toxicity in dopaminergic cells.
authors.affiliation: Department of Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Casanova 143, E-08036 Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.forename: Gemma
authors.initials: G
authors.lastname: Trias
authors.forename: Miquel
authors.initials: M
authors.lastname: Bernardo
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D013454:Sulfoxides; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D017392:Thiobarbituric Acid Reactive Substances; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase; C016766:sulforaphane; D005978:Glutathione; D004298:Dopamine