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

• Published in: Toxicology in vitro 2009-03, Vol.23 (2), p.302-307
• Main Authors: Roos, Daniel H., Puntel, Robson L., Santos, Matheus M., Souza, Diogo O.G., Farina, Marcelo, Nogueira, Cristina W., Aschner, Michael, Burger, Marilise Escobar, Barbosa, Nilda B.V., Rocha, João B.T.
• Format: Article
• Language: English
• Subjects: Animals; Azoles - pharmacology; Benzene Derivatives - pharmacology; Brain - drug effects; Brain - metabolism; Cell Survival - drug effects; Dizocilpine Maleate - pharmacology; Drug Combinations; Free radicals; Glutamatergic system; Glutamic Acid - metabolism; Guanosine - pharmacology; L-Lactate Dehydrogenase - metabolism; Male; MeHg; Methylmercury Compounds - toxicity; Organ Culture Techniques; Organoselenium Compounds - pharmacology; Oxidative Stress - drug effects; Rats; Rats, Wistar
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2008.12.020

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.