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 Citations (Scopus)

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
StatePublished - 2012
Externally publishedYes

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Selenoproteins
Thioredoxin-Disulfide Reductase
Peroxiredoxins
Glutathione Peroxidase
Liver
Glutathione Reductase
Brain
Sulfhydryl Compounds
Oxidative stress
Superoxide Dismutase
Toxicity
Oxidative Stress
Porphobilinogen Synthase
Enzymes
Catalase
Lipid Peroxidation
Oxidation-Reduction
Weight Loss
Proteins
Blood

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

Diphenyl ditelluride targets brain selenoproteins in vivo : Inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. / Comparsi, Bruna; Meinerz, Daiane F.; Franco, Jeferson L.; Posser, Thaís; De Souza Prestes, Alessandro; Stefanello, Sílvio Terra; Dos Santos, Danúbia B.; Wagner, Caroline; Farina, Marcelo; Aschner, Michael; Dafre, Alcir L.; Rocha, João B T.

In: Molecular and Cellular Biochemistry, Vol. 370, No. 1-2, 2012, p. 173-182.

Research output: Contribution to journalArticle

Comparsi, B, Meinerz, DF, Franco, JL, Posser, T, De Souza Prestes, A, Stefanello, ST, Dos Santos, DB, Wagner, C, Farina, M, Aschner, M, Dafre, AL & Rocha, JBT 2012, 'Diphenyl ditelluride targets brain selenoproteins in vivo: Inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure', Molecular and Cellular Biochemistry, vol. 370, no. 1-2, pp. 173-182. https://doi.org/10.1007/s11010-012-1408-6
Comparsi, Bruna ; Meinerz, Daiane F. ; Franco, Jeferson L. ; Posser, Thaís ; De Souza Prestes, Alessandro ; Stefanello, Sílvio Terra ; Dos Santos, Danúbia B. ; Wagner, Caroline ; Farina, Marcelo ; Aschner, Michael ; Dafre, Alcir L. ; Rocha, João B T. / Diphenyl ditelluride targets brain selenoproteins in vivo : Inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. In: Molecular and Cellular Biochemistry. 2012 ; Vol. 370, No. 1-2. pp. 173-182.
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AU - Comparsi, Bruna

AU - Meinerz, Daiane F.

AU - Franco, Jeferson L.

AU - Posser, Thaís

AU - De Souza Prestes, Alessandro

AU - Stefanello, Sílvio Terra

AU - Dos Santos, Danúbia B.

AU - Wagner, Caroline

AU - Farina, Marcelo

AU - Aschner, Michael

AU - Dafre, Alcir L.

AU - Rocha, João B T

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