Guanosine and synthetic organoselenium compounds modulate methylmercury-induced oxidative stress in rat brain cortical slices: involvement of oxidative stress and glutamatergic system.
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 microM) increased 2',7'-dichlorodihydrofluorescin (DCFH) oxidation after 2h of exposure. At 50 microM, MeHg increased DCFH oxidation only after 5h of exposure. Guanosine (1 and 5 microM) did not caused any effect per se; however, it blocked the increase in DCFH caused by 200 or 50 microM MeHg. Ebselen (5 and 10 microM) decreased significantly the DCFH oxidation after 2 and 5h of exposure to MeHg. Diphenyl diselenide (5 microM) 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.
Roos
Daniel H
DH
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Puntel
Robson L
RL
Santos
Matheus M
MM
Souza
Diogo O G
DO
Farina
Marcelo
M
Nogueira
Cristina W
CW
Aschner
Michael
M
Burger
Marilise Escobar
ME
Barbosa
Nilda B V
NB
Rocha
João B T
JB
D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004338:Drug Combinations; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D009924:Organ Culture Techniques; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D001393:Azoles; D001555:Benzene Derivatives; D004338:Drug Combinations; D054833:Isoindoles; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; D006151:Guanosine; C061132:diphenyldiselenide; D018698:Glutamic Acid; C042986:ebselen; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase