Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure

Abstract

In this study, we investigated the effect of diphenyl ditelluride (PhTe)(2) administration (10 and 50 μmol/kg) on adult mouse behavioral performance as well as several parameters of oxidative stress in the brain and liver. Adult mice were injected with (PhTe)(2) or canola oil subcutaneously (s.c.) daily for 7 days. Results demonstrated that (PhTe)(2) induced prominent signs of toxicity (body weight loss), behavioral alterations and increased in lipid peroxidation in brain. 50 μmol/kg (PhTe)(2) inhibited blood δ-aminolevulinic acid dehydratase (δ-ALA-D), a redox sensitive enzyme. (PhTe)(2) caused an increase in cerebral non-protein thiol (NPSH) and protein thiol (PSH) groups. In the liver, 50 μmol/kg (PhTe)(2) decreased NPSH, but did not alter the content of protein thiol groups. (PhTe)(2) decreased cerebral antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and thioredoxin reductase (TrxR). In liver, (PhTe)(2) increase SOD and GR and decreased GPx activity. Results obtained herein suggest that the brain was more susceptible to oxidative stress induced by (PhTe)(2) than the liver. Furthermore, we have demonstrated for the first time that TrxR is an in vivo target for (PhTe)(2.) Combined, these results highlight a novel molecular mechanism involved in the toxicity of (PhTe)(2). In particular the inhibition of important selenoenzymes (TrxR and GPx) seems to be involved in the neurotoxicity associated with (PhTe)(2) exposure in adult mice.

Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

“…Thus, in view of its big size, tellurium behaves more as redox active metal than a nonmetal. This explains the ability of its cationic forms to oxidize thiolates and possibly selenolates [52–57]. In a similar way to selenite (Se(IV)), tellurite can inhibit thiol containing enzymes and this can be the molecular basis of tellurium toxicity (Figure 2).…”

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

“…The nanoenzyme showed higher efficiency and provided a platform for the synthesis and designing of polymeric nanoparticles as excellent model of enzyme mimics (Huang et al, 2008). Organotellurium vitro models of animal pathologies (Maciel et al, 2000;Taylor, 1996;Stangherlin et al, 2009;Moretto et al, 2007;Heimfarth et al, 2011;Heimfarth et al, 2012 b;Comparsi et al, 2012).…”

“…In effect, diphenyl ditelluride (PhTe)2 was found to be extremely toxic to mice and rats after acute or chronic exposure (Maciel et al, 2000;Heimfarth et al, 2012 b ;Comparsi et al, 2012). The toxicity of tellurides can be associated with their pro-oxidant activity, particularly, the oxidation of thiol-and selenolgroups of proteins (Nogueira, Zeni & Rocha, 2004;Comparsi et al 2012;Hassan & Rocha 2012).…”

“…The toxicity of tellurides can be associated with their pro-oxidant activity, particularly, the oxidation of thiol-and selenolgroups of proteins (Nogueira, Zeni & Rocha, 2004;Comparsi et al 2012;Hassan & Rocha 2012). …”

“…Similarly,organoselenides and tellurides can be toxic in different in vivo and in vitro models of animal pathologies (Maciel et al, 2000;Taylor, 1996;Stangherlin et al, 2009;Moretto et al, 2007;Heimfarth et al, 2011;Heimfarth et al, 2012 b;Comparsi et al, 2012). In effect, diphenyl ditelluride (PhTe)2 was found to be extremely toxic to mice and rats after acute or chronic exposure (Maciel et al, 2000;Heimfarth et al, 2012 b ;Comparsi et al, 2012). The toxicity of tellurides can be associated with their pro-oxidant activity, particularly, the oxidation of thiol-and selenol-groups of proteins (Nogueira, Zeni & Rocha, 2004;Comparsi et al 2012;Hassan & Rocha 2012).…”