Diphenyl diselenide protects against methylmercury-induced inhibition of thioredoxin reductase and glutathione peroxidase in human neuroblastoma cells: a comparison with ebselen

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)₂ and 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)₂ 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 μm). Among the selenocompounds only (PhSe)₂ significantly protected against the effects of MeHg on GPx activity. Taken together, these results indicate a potential use for ebselen and (PhSe)₂ against MeHg toxicity. Furthermore, for the first time, we have demonstrated that (PhSe)₂ 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.