title: Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neurotoxicity mouse model.
abstract: Interest in biochemistry of organoselenium compound has increased in the last decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)2 (5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)2. After the treatment (21 days), the animals were killed and the cerebral cortex was analyzed. Electron microscopy indicated an enlarged and fused mitochondria leading to a reduced number of organelles, in the MeHg-exposed mice. Furthermore, cortical creatine kinase activity, a sensitive mitochondrial oxidative stress sensor, was almost abolished by MeHg. Subcutaneous (PhSe)2 co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)2 also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)2 alone. Mechanistically, (PhSe)2 (1 μM; 24 h) would trigger the cytoprotective Nrf-2 pathway for activating target genes, since astroglial cells exposed to the chalcogen showed increased content of hemeoxygenase type 1, a sensitive marker of the activation of this via. Thus, it is proposed that the (PhSe)2-neuroprotective effect might be linked to its mitoprotective activity.
authors.affiliation: Laboratório de Bioenergética e Estresse Oxidativo, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Córrego Grande, Bloco C-201/214, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Glaser
authors.forename: Roberta de Paula
authors.initials: Rde P
authors.lastname: Martins
authors.forename: Ana Julia Hoffmann
authors.initials: AJ
authors.lastname: Vieira
authors.forename: Eliana de Medeiros
authors.initials: Ede M
authors.lastname: Oliveira
authors.forename: Marcos Raniel
authors.initials: MR
authors.lastname: Straliotto
authors.forename: Jorge Humberto
authors.initials: JH
authors.lastname: Mukdsi
authors.forename: Alicia Inés
authors.initials: AI
authors.lastname: Torres
authors.forename: Andreza Fabro
authors.initials: AF
authors.lastname: de Bem
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: De Paul
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008297:Male; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism / Q000473:pathology; D008767:Methylmercury Compounds / Q000633:toxicity; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D001555:Benzene Derivatives; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; C061132:diphenyldiselenide; D051547:Heme Oxygenase-1