Ebselen and diorganylchalcogenides decrease in vitro glutamate uptake by rat brain slices: prevention by DTT and GSH.
The purpose of this study was to investigate the possible involvement of the glutamatergic system in the neurotoxicity of diorganylchalcogenides or organochalcogenides from slices of cerebral cortex in different ages of development: 12- and 60-day-old rats. Glutamate uptake was evaluated in cortical slices of 12 and 60 days old rats. Cortex slices were incubated with three different organochalcogenides with or without reduced glutathione or dithiothreitol. At 100 microM, ebselen, diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in vitro inhibited the [3H]glutamate uptake in both age. Both 60-day-old rats and for 12-day-old rats, GSH and DTT prevented the (PhTe)2-induced inhibition of glutamate uptake but did not protect the inhibition caused by ebselen and (PhSe)2. These findings suggest that the neurotoxicity of organochalcogenides could be related to their effects on brain glutamate uptake, conceivably involving a redox modulation of reactive amino acids from the glutamate transporter proteins.
Moretto
M B
MB
Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. beatriz@smail.ufsm.br
Thomazi
A P
AP
Godinho
G
G
Roessler
T M
TM
Nogueira
C W
CW
Souza
D O
DO
Wofchuk
S
S
Rocha
J B T
JB
D000375:Aging / Q000502:physiology; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001393:Azoles / Q000633:toxicity*; D001555:Benzene Derivatives / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018011:Chalcogens / Q000633:toxicity*; D004229:Dithiothreitol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D066298:In Vitro Techniques; D054833:Isoindoles; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D000931:Antidotes; D001393:Azoles; D001555:Benzene Derivatives; D018011:Chalcogens; D054833:Isoindoles; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; D018698:Glutamic Acid; C042986:ebselen; D005978:Glutathione; D004229:Dithiothreitol