title: Diphenyl diselenide protects against methylmercury-induced inhibition of thioredoxin reductase and glutathione peroxidase in human neuroblastoma cells: a comparison with ebselen.
abstract: Exposure to methylmercury (MeHg), an important environmental toxicant, may lead to serious health risks, damaging various organs and predominantly affecting the brain function. The toxicity of MeHg can be related to the inhibition of important selenoenzymes, such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). Experimental studies have shown that selenocompounds play an important role as cellular detoxifiers and protective agents against the harmful effects of mercury. The present study investigated the mechanisms by which diphenyl diselenide [(PhSe)2] and ebselen interfered with the interaction of mercury (MeHg) and selenoenzymes (TrxR and GPx) in an in vitro experimental model of cultured human neuroblastoma cells (SH-SY5Y). Our results established that (PhSe)2and ebselen increased the activity and expression of TrxR. In contrast, MeHg inhibited TrxR activity even at low doses (0.5 μm). Coexposure to selenocompounds and MeHg showed a protective effect of (PhSe)2on both the activity and expression of TrxR. When selenoenzyme GPx was evaluated, selenocompounds did not alter its activity or expression significantly, whereas MeHg inhibited the activity of GPx (from 1 μm). Among the selenocompounds only (PhSe)2significantly protected against the effects of MeHg on GPx activity. Taken together, these results indicate a potential use for ebselen and (PhSe)2against MeHg toxicity. Furthermore, for the first time, we have demonstrated that (PhSe)2caused a more pronounced upregulation of TrxR than ebselen in neuroblastoma cells, likely reflecting an important molecular mechanism involved in the antioxidant properties of this compound. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
authors.forename: Daiane F
authors.initials: DF
authors.lastname: Meinerz
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
authors.forename: Vasco
authors.initials: V
authors.lastname: Branco
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
authors.forename: João Batista T
authors.identifier: 0000-0003-3829-0595
authors.initials: JBT
authors.lastname: Rocha
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054833:Isoindoles; D008767:Methylmercury Compounds / Q000633:toxicity*; D009447:Neuroblastoma / Q000139:chemically induced / Q000188:drug therapy; D016566:Organoselenium Compounds / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D001393:Azoles; D001555:Benzene Derivatives; D054833:Isoindoles; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; C042986:ebselen; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase
keywords: Ebselen; diphenyl diselenide; glutathione peroxidase; methylmercury; neuroblastoma cells; thioredoxin reductase