title: Diphenyl ditelluride targets brain selenoproteins in vivo: inhibition of cerebral thioredoxin reductase and glutathione peroxidase in mice after acute exposure.
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.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Comparsi
authors.forename: Daiane F
authors.initials: DF
authors.lastname: Meinerz
authors.forename: Jeferson L
authors.initials: JL
authors.lastname: Franco
authors.forename: Thaís
authors.initials: T
authors.lastname: Posser
authors.forename: Alessandro de Souza
authors.initials: Ade S
authors.lastname: Prestes
authors.forename: Sílvio Terra
authors.initials: ST
authors.lastname: Stefanello
authors.forename: Danúbia B
authors.initials: DB
authors.lastname: dos Santos
authors.forename: Caroline
authors.initials: C
authors.lastname: Wagner
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.forename: Alcir L
authors.initials: AL
authors.lastname: Dafre
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D045442:Rotarod Performance Test; D051140:Selenoproteins / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001555:Benzene Derivatives; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D051140:Selenoproteins; D013438:Sulfhydryl Compounds; C434247:diphenylditelluride; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; D000623:Porphobilinogen Synthase