Ebselen protects against methylmercury-induced inhibition of glutamate uptake by cortical slices from adult mice.
Methylmercury (MeHg) is a highly neurotoxic compound and the inhibition of glutamate uptake by astrocytes has been pointed as an important mechanism involved in MeHg-induced glutamate excitotoxicity. We examined the effect of oral exposure to MeHg (10 and 40 mg/l in drinking water) on glutamate uptake by brain cortical slices of adult mice. Moreover, the possible protective role of ebselen (20 mg/kg, subcutaneously) against MeHg effect was also examined. In addition, it was measured the glutathione peroxidase and catalase activities in mice brain. Our results demonstrated, for the first time, that in vivo exposure to MeHg causes a dose-dependent decrease in glutamate uptake and that ebselen, which did not affect the uptake per se, reverted this effect. MeHg decreased glutathione peroxidase activity and increased catalase activity, effects which were also prevented by ebselen. These results may indirectly indicate that: (i) the in vivo inhibitory effect of MeHg on glutamate uptake could be probably related to overproduction of H(2)O(2); (ii) the protective effect of ebselen on MeHg-induced inhibition of glutamate uptake could be related to its ability to detoxify H(2)O(2).
Farina
Marcelo
M
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo CEP, 90035-003 Porto Alegre, RS, Brazil. marcelofarina@zipmail.com.br
Frizzo
Marcos E S
ME
Soares
Félix A A
FA
Schwalm
Fábio D
FD
Dietrich
Marcelo O
MO
Zeni
Gilson
G
Rocha
João B T
JB
Souza
Diogo O
DO
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000502:physiology; D001393:Azoles / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002540:Cerebral Cortex / Q000473:pathology / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics*; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide; D054833:Isoindoles; D015227:Lipid Peroxidation; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; D018698:Glutamic Acid; C042986:ebselen; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase