title: Antioxidant properties of atypical antipsychotic drugs used in the treatment of schizophrenia.
abstract: The aim of this study was to compare the antioxidant activities of six atypical antipsychotic drugs: clozapine (CLZ), quetiapine, olanzapine (OLA), risperidone, ziprasidone, aripiprazole (ARI), as well as a typical antipsychotic drug, haloperidol. Several tests of antioxidant activity were used: protection of thiol groups against oxidation by peroxynitrite (PN) and 3-morpholinosydnonimine (SIN-1, generator of PN), oxidation of dihydrorhodamine 123 by PN, SIN-1 and hypochlorite (NaOCl), bleaching of fluorescein fluorescence by PN, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH, generator of peroxyl radicals) and NaOCl, radical-scavenging activity with respect to 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) radical, 2,2-diphenyl-1-picrylhydrazyl free radical and the Ferric Reducing Antioxidant Potential. In most of the tests, OLA showed the highest antioxidant activity, followed by CLZ and in some cases ARI, other compounds being much less active or not active. OLA and CLZ exerted limited toxicity on mouse neuroblastoma Neuro-2A (N2A) cells and protected the cells against the toxic action of SIN-1, AAPH and NaOCl in the physiologically relevant concentration range of these oxidants. Both drugs reduced the PN-induced nitration of intracellular proteins. Given that schizophrenia is associated with oxidative and nitrosative stress, the direct antioxidant activity OLA and CLZ may contribute to the therapeutic action of these compounds.
authors.affiliation: Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszow, Zelwerowicza St. 4, PL 35-601 Rzeszow, Poland. Electronic address: isadowska@poczta.fm.
authors.forename: Izabela
authors.initials: I
authors.lastname: Sadowska-Bartosz
authors.affiliation: Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszow, Zelwerowicza St. 4, PL 35-601 Rzeszow, Poland.
authors.forename: Sabina
authors.initials: S
authors.lastname: Galiniak
authors.affiliation: Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszow, Zelwerowicza St. 4, PL 35-601 Rzeszow, Poland; Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Bartosz
authors.affiliation: Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Zuberek
authors.affiliation: Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grzelak
authors.affiliation: Department of Biological Psychiatry of the Chair of Experimental and Clinical Physiology, Medical University of Lodz, Mazowiecka St. 6/8, 92-215 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dietrich-Muszalska
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents
keywords: Antipsychotics; Clozapine; Nitrosative stress; Olanzapine; Oxidative stress; Schizophrenia