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Ebselen and diorganylchalcogenides decrease in vitro glutamate uptake by rat brain slices: prevention by DTT and GSH
M B Moretto1, A P Thomazi, G Godinho
1Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. beatriz@smail.ufsm.br
Abstract:
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.
Insights
Organochalcogenides like ebselen and diphenyl diselenide impair brain glutamate uptake, suggesting neurotoxicity linked to glutamate transport. Glutathione and dithiothreitol protected against some, but not all, of these effects.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Organochalcogenides are compounds containing selenium or tellurium.
- The glutamatergic system plays a crucial role in neurotransmission and neuronal function.
- Neurotoxicity of organochalcogenides is not fully understood, particularly concerning their impact on glutamate uptake.
Purpose of the Study:
- To investigate the neurotoxic effects of specific organochalcogenides on glutamate uptake in rat cerebral cortex.
- To determine if these effects differ between young (12-day-old) and adult (60-day-old) rats.
- To explore the potential role of redox modulation in organochalcogenide-induced neurotoxicity.
Main Methods:
- Cortical slices from 12- and 60-day-old rats were used.
- Glutamate uptake was measured using [3H]glutamate.
- Slices were incubated with ebselen, diphenyl diselenide ((PhSe)2), and diphenyl ditelluride ((PhTe)2) with or without reduced glutathione (GSH) or dithiothreitol (DTT).
Main Results:
- Ebselen, (PhSe)2, and (PhTe)2 at 100 microM inhibited [3H]glutamate uptake in both age groups.
- GSH and DTT protected against (PhTe)2-induced inhibition.
- GSH and DTT did not protect against the inhibition caused by ebselen and (PhSe)2.
Conclusions:
- Organochalcogenide neurotoxicity may involve the disruption of brain glutamate uptake.
- The mechanism of neurotoxicity appears to involve redox modulation of glutamate transporter proteins.
- Differential protective effects of GSH and DTT suggest distinct mechanisms of action for different organochalcogenides.
