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

Bruna Comparsi, Daiane F. Meinerz, Jeferson L. Franco, Thaís Posser, Alessandro De Souza Prestes, Sílvio Terra Stefanello, Danúbia B. Dos Santos, Caroline Wagner, Marcelo Farina, Michael Aschner, Alcir L. Dafre, João B T Rocha

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume370
Issue number1-2
DOIs
Publication statusPublished - 2012
Externally publishedYes

    Fingerprint

Keywords

  • Antioxidant enzymes
  • Diphenyl ditelluride
  • Glutathione peroxidase (GPx)
  • Organotellurium compounds
  • Oxidative stress
  • Thioredoxin reductase (TrxR)
  • Toxicity

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this