TY - JOUR
T1 - Diphenyl ditelluride targets brain selenoproteins in vivo
T2 - Inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure
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.
N1 - Funding Information:
Acknowledgments This study was supported by grants from CAPES, FINEP-IBNet, FAPERGS-PRONEX, INCT-CNPq for Ex-citotoxicity and Neuroprotection and CNPq.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - Antioxidant enzymes
KW - Diphenyl ditelluride
KW - Glutathione peroxidase (GPx)
KW - Organotellurium compounds
KW - Oxidative stress
KW - Thioredoxin reductase (TrxR)
KW - Toxicity
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U2 - 10.1007/s11010-012-1408-6
DO - 10.1007/s11010-012-1408-6
M3 - Article
C2 - 22886391
AN - SCOPUS:84984555034
SN - 0300-8177
VL - 370
SP - 173
EP - 182
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -