Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: Involvement of oxidative stress and glutamatergic system

Daniel H. Roos, Robson L. Puntel, Matheus M. Santos, Diogo O.G. Souza, Marcelo Farina, Cristina W. Nogueira, Michael Aschner, Marilise Escobar Burger, Nilda B.V. Barbosa, João B.T. Rocha

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Excessive formation of reactive oxygen species (ROS) and disruption of glutamate uptake have been pointed as two key mechanisms in methylmercury-toxicity. Thus, here we investigate the involvement of glutamatergic system in methylmercury (MeHg) neurotoxicity and whether diphenyl diselenide, ebselen and guanosine could protect cortical rat brain slices from MeHg-induced ROS generation. MeHg (100 and 200 μM) increased 2′,7′-dichlorodihydrofluorescin (DCFH) oxidation after 2 h of exposure. At 50 μM, MeHg increased DCFH oxidation only after 5 h of exposure. Guanosine (1 and 5 μM) did not caused any effect per se; however, it blocked the increase in DCFH caused by 200 or 50 μM MeHg. Ebselen (5 and 10 μM) decreased significantly the DCFH oxidation after 2 and 5 h of exposure to MeHg. Diphenyl diselenide (5 μM) did not change the basal DCFH oxidation, but abolished the pro-oxidant effect of MeHg. MK-801 also abolished the pro-oxidant effect of MeHg. These results demonstrate for the first time the potential antioxidant properties of organoseleniun compounds and guanosine against MeHg-induced ROS generation after short-term exposure in a simple in vitro model. In conclusion, endogenous purine (guanosine) and two synthetic organoselenium compounds can modulate the pro-oxidant effect of MeHg in cortical brain slices.

Original languageEnglish (US)
Pages (from-to)302-307
Number of pages6
JournalToxicology in Vitro
Volume23
Issue number2
DOIs
StatePublished - Mar 2009
Externally publishedYes

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Keywords

  • Free radicals
  • Glutamatergic system
  • MeHg

ASJC Scopus subject areas

  • Toxicology

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