title: Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects.
abstract: Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Sílvio Terra
authors.initials: ST
authors.lastname: Stefanello
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dobrachinski
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Nélson Rodrigues
authors.initials: NR
authors.lastname: de Carvalho
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Guilherme Pires
authors.initials: GP
authors.lastname: Amaral
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Rômulo Pillon
authors.initials: RP
authors.lastname: Barcelos
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Vitor Antunes
authors.initials: VA
authors.lastname: Oliveira
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Cláudia Sirlene
authors.initials: CS
authors.lastname: Oliveira
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Camila Ferrazza Alves
authors.initials: CF
authors.lastname: Giordani
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Pereira
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Oscar Endrigo Dorneles
authors.initials: OE
authors.lastname: Rodrigues
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors.forename: Félix Alexandre Antunes
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009599:Nitroprusside / Q000737:chemistry / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000737:chemistry / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D001555:Benzene Derivatives; D016166:Free Radical Scavengers; D053769:Nanocapsules; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D009599:Nitroprusside; D000623:Porphobilinogen Synthase
keywords: DPDS-NCS; antioxidant properties; diphenyl diselenide; lipid peroxidation; δ-ALA-D