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) ] 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) 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) 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) significantly protected against the effects of MeHg on GPx activity. Taken together, these results indicate a potential use for ebselen and (PhSe) against MeHg toxicity. Furthermore, for the first time, we have demonstrated that (PhSe) 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 © 2017 John Wiley & Sons, Ltd.

Diphenyl diselenide protects neuronal cells against oxidative stress and mitochondrial dysfunction: Involvement of the glutathione-dependent antioxidant system

“…We can suppose that Gpx1 isoform would be preferentially synthetized in (PhSe) 2 -treated HT22 cells, suggesting an interplay between the different isoforms and also suggest that (PhSe) 2 regulates Gpx1 -specific transcriptional machinery in HT22 cells that does not involve Gpx4 . Contrary to our results, (PhSe) 2 did not increase the GPx activity and protein expression in neuroblastoma cells [61] , indicating that these cells would present a different physiological response than those found in HT22 cells. Together these evidences reinforce the idea that this simple organoselenium compound acts as an indirect and effective antioxidant by modulating intracellular redox-sensitive responses.…”

Depletion of multidrug‐resistant uropathogenic Escherichia coli BC1 by ebselen and silver ion

“…In addition, when ebselen and silver ion were used together, the ALT level showed no difference from that of the control group. This is because ebselen was able to alleviate the liver damage from different causes 57,58 and reduce the toxicity of heavy metals caused by methylmercury and manganese chloride in vivo, including silver ion 22,59 . The increase in blood urea has many causes, and it is not as useful a biomarker as serum creatinine for reflecting renal function.…”

The Catecholaminergic Neurotransmitter System in Methylmercury-Induced Neurotoxicity

“…Indeed, many studies have corroborated the ability of MeHg to inhibit selenoenzymes, both in vitro and after in vivo exposure (Carvalho et al, 2008;Franco et al, 2009;Wagner et al, 2010;Branco et al, 2011;2014Dalla Corte et al, 2013;Meinerz et al, 2017).…”