DIPHENYL DISELENIDE ADMINISTRATION ENHANCES CORTICAL MITOCHONDRIAL NUMBER AND ACTIVITY BY INCREASING HEMEOXYGENASE TYPE 1CONTENT IN A METHYLMERCURY-INDUCED NEUROTOXICITY MOUSE MODEL

VIVIANE GLASER; ROBERTA DE PAULA MARTINS; ANA JULIA HOFFMANN VIEIRA; ELIANA DE MEDEIROS OLIVEIRA; MARCOS RANIEL STRALIOTTO; JORGE MUKDSI; ALICIA TORRES; ANDREZA FABRO DE BEM; MARCELO FARINA; JOÃO BATISTA TEIXEIRA DA ROCHA; ANA LUCIA DE PAUL; ALEXANDRA LATINI

MOLECULAR AND CELLULAR BIOCHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2014 vol. 390 p. 1 - 8

0300-8177

Interest in biochemistry of organo selenium 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 ìmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)2 (5ìmol/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 analyzed. Electron microscopy indicated 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 ìM; 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 the (PhSe)2-neuroprotective effect might be linked to its mitoprotective activity.