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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)<jats:sub>2<\/jats:sub>] and ebselen interfered with the interaction of mercury (MeHg) and selenoenzymes (TrxR and GPx) in an <jats:italic>in vitro<\/jats:italic> experimental model of cultured human neuroblastoma cells (SH\u2010SY5Y). Our results established that (PhSe)<jats:sub>2<\/jats:sub> and ebselen increased the activity and expression of TrxR. In contrast, MeHg inhibited TrxR activity even at low doses (0.5\u2009\u03bc<jats:sc>m<\/jats:sc>). Coexposure to selenocompounds and MeHg showed a protective effect of (PhSe)<jats:sub>2<\/jats:sub> on 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\u2009\u03bc<jats:sc>m<\/jats:sc>). Among the selenocompounds only (PhSe)<jats:sub>2<\/jats:sub> significantly protected against the effects of MeHg on GPx activity. Taken together, these results indicate a potential use for ebselen and (PhSe)<jats:sub>2<\/jats:sub> against MeHg toxicity. Furthermore, for the first time, we have demonstrated that (PhSe)<jats:sub>2<\/jats:sub> caused 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 \u00a9 2017 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3458","type":"journal-article","created":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T05:24:46Z","timestamp":1491456286000},"page":"1073-1081","source":"Crossref","is-referenced-by-count":37,"title":["Diphenyl diselenide protects against methylmercury\u2010induced inhibition of thioredoxin reductase and glutathione peroxidase in human neuroblastoma cells: a comparison with ebselen"],"prefix":"10.1002","volume":"37","author":[{"given":"Daiane F.","family":"Meinerz","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Biologia Molecular, Centro de Ci\u00eancias Naturais e Exatas Universidade Federal de Santa Maria  97105\u2010900 Santa Maria RS Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasco","family":"Branco","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) Faculty of Pharmacy, Universidade de Lisboa  Av. 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