De Paula Martins R.,Federal University of Santa Catarina |
Glaser V.,Federal University of Santa Catarina |
Da Luz Scheffer D.,Federal University of Santa Catarina |
De Paula Ferreira P.M.,Federal University of Santa Catarina |
And 6 more authors.
Journal of Bioenergetics and Biomembranes
Interactions of chemicals with cerebral cellular systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells, including platelets and/or peripheral blood lymphocytes. Therefore, here it was investigated whether peripheral blood markers may be useful for assessing the central toxic effects of methylmercury (MeHg). For this purpose, we investigated platelet mitochondrial physiology in a well-established mouse model of MeHg-induced neurotoxicity, and correlated this peripheral activity with behavioural and central biochemical parameters. In order to characterize the cortical toxicity induced by MeHg (20 and 40 mg/L in drinking water, 21 days), the behavioral parameter namely, short-term object recognition, and the central mitochondrial impairment assessed by measuring respiratory complexes I-IV enzyme activities were determined in MeHg-poisoned animals. Neurotoxicity induced by MeHg exposure provoked compromised cortical activity (memory impairment) and reduced NADH dehydrogenase, complex II and II-III activities in the cerebral cortex. These alterations correlated with impaired systemic platelet oxygen consumption of intoxicated mice, which was characterized by reduced electron transfer activity and uncoupled mitochondria. The data brought here demonstrated that impaired systemic platelet oxygen consumption is a sensitive and non-invasive marker of the brain energy deficits induced by MeHg poisoning. Finally, brain and platelets biochemical alterations significantly correlated with cognitive behavior in poisoned mice. Therefore, it could be proposed the use of platelet oxygen consumption as a peripheral blood marker of brain function in a mouse model MeHg-induced neurotoxicity. © 2013 Springer Science+Business Media New York. Source
Glaser V.,Campus Universitario Corrego Grande |
Martins R.D.P.,Campus Universitario Corrego Grande |
Vieira A.J.H.,Campus Universitario Corrego Grande |
Oliveira E.D.M.,Federal University of Santa Catarina |
And 8 more authors.
Molecular and Cellular Biochemistry
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. © 2014 Springer Science+Business Media New York. Source