title: Protective effects of diphenyl diselenide in a mouse model of brain toxicity.
abstract: Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neurotoxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II-III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neurotoxicity induced by brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe)2 was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe)2 effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe)2 could be consider as a neuroprotectant compound to be tested under neurotoxicity.
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors: Viviane
authors: V
authors: Glaser
authors: Bettina
authors: B
authors: Moritz
authors: Ariana
authors: A
authors: Schmitz
authors: Alcir Luiz
authors: AL
authors: Dafré
authors: Evelise Maria
authors: EM
authors: Nazari
authors: Yara Maria
authors: YM
authors: Rauh Müller
authors: Luciane
authors: L
authors: Feksa
authors: Marcos Raniel
authors: MR
authors: Straliottoa
authors: Andreza Fabro
authors: AF
authors: de Bem
authors: Marcelo
authors: M
authors: Farina
authors: João Batista Teixeira
authors: JB
authors: da Rocha
authors: Alexandra
authors: A
authors: Latini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D008297:Male; D008767:Methylmercury Compounds / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C061132:diphenyldiselenide
keywords: Diphenyl diselenide; Methylmercury; Neurotoxicity; Oxidative stress; Respiratory chain complexes