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

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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.

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Acknowledgments

This study was supported by grants from CAPES, FINEP-IBNet, FAPERGS-PRONEX, INCT-CNPq for Excitotoxicity and Neuroprotection and CNPq.

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Authors and Affiliations

  1. Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil

    Bruna Comparsi, Daiane F. Meinerz, Alessandro de Souza Prestes, Sílvio Terra Stefanello & João B. T. Rocha

  2. Universidade Federal do Pampa, Campus São Gabriel, Sao Gabriel, RS, CEP 97300-000, Brazil

    Jeferson L. Franco & Thaís Posser

  3. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianopolis, SC, CEP 88040-900, Brazil

    Danúbia B. dos Santos, Marcelo Farina & Alcir L. Dafre

  4. Universidade Federal do pampa, Campus de Caçapava do Sul, Caçapava do Sul, RS, CEP 96570-000, Brazil

    Caroline Wagner

  5. Departments of Pediatrics and Pharmacology, Neuroscience Graduate Program, Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Michael Aschner

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  1. Bruna Comparsi
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  2. Daiane F. Meinerz
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  3. Jeferson L. Franco
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  6. Sílvio Terra Stefanello
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  12. João B. T. Rocha
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Correspondence to Jeferson L. Franco or João B. T. Rocha.

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Comparsi, B., Meinerz, D.F., Franco, J.L. et al. Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure. Mol Cell Biochem 370, 173–182 (2012). https://doi.org/10.1007/s11010-012-1408-6

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