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

作者：Comparsi Bruna; Meinerz Daiane F; Franco Jeferson L^*; Posser Thais; Prestes Alessandro de Souza; Stefanello Silvio Terra; dos Santos Danubia B; Wagner Caroline; Farina Marcelo; Aschner Michael; Dafre Alcir L; Rocha Joao B T

来源：Molecular and Cellular Biochemistry, 2012, 370(1-2): 173-182.

DOI：10.1007/s11010-012-1408-6

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

In this study, we investigated the effect of diphenyl ditelluride (PhTe)(2) administration (10 and 50 mu mol/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 mu mol/kg (PhTe)(2) inhibited blood delta-aminolevulinic acid dehydratase (delta-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 mu mol/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.

• 出版日期2012-11