Diphenyl diselenide administration enhances cortical mitochondrial number and activity by increasing hemeoxygenase type 1 content in a methylmercury-induced neurotoxicity mouse model

• Published in: Molecular and cellular biochemistry Vol. 390; no. 1-2; pp. 1 - 8
• Main Authors: Glaser, Viviane, Martins, Roberta de Paula, Vieira, Ana Julia Hoffmann, Oliveira, Eliana de Medeiros, Straliotto, Marcos Raniel, Mukdsi, Jorge Humberto, Torres, Alicia Inés, de Bem, Andreza Fabro, Farina, Marcelo, da Rocha, João Batista Teixeira, De Paul, Ana Lucia, Latini, Alexandra
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-05-2014; Springer; Springer Nature B.V
• Subjects: Animals; Benzene Derivatives - administration & dosage; Biochemistry; Biomedical and Life Sciences; Brain; Brain - metabolism; Brain - pathology; Cardiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Disease Models, Animal; Drinking water; Heme Oxygenase-1 - biosynthesis; Kinases; Life Sciences; Male; Medical Biochemistry; Mercury; Mercury Poisoning, Nervous System - metabolism; Mercury Poisoning, Nervous System - pathology; Methylmercury; Methylmercury Compounds - toxicity; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; Neurotoxicity; Oncology; Organoselenium Compounds - administration & dosage; Oxidative stress; Oxidative Stress - drug effects; Rodents; Diphenyl diselenide; Hemeoxygenase type 1; Mitochondrial morphology; Creatine kinase; Methylmercury
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1870-9

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)
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(5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Swiss male mice were divided into four experimental groups: control, (PhSe)
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(5 μmol/kg, subcutaneous administration), MeHg (40 mg/L, in tap water), and MeHg + (PhSe)
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. 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)
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co-treatment rescued from MeHg-induced mitochondrial alterations. (PhSe)
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also behaved as an enhancer of mitochondrial biogenesis, by increasing cortical mitochondria content in mouse-receiving (PhSe)
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alone. Mechanistically, (PhSe)
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(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)
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-neuroprotective effect might be linked to its mitoprotective activity.