Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content 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 Humberto Mukdsi, Alicia Inés Torres, Andreza Fabro De Bem, Marcelo Farina, João Batista Teixeira Da Rocha, Ana Lucia De Paul, Alexandra Latini*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume390
Issue number1-2
DOIs
Publication statusPublished - May 2014
Externally publishedYes

Keywords

  • diphenyl diselenide
  • methylmercury
  • mitochondrial morphology
  • creatine kinase
  • hemeoxygenase type 1

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