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Related Experiment Videos

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

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|February 27, 2007
PubMed
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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.

Related Experiment Videos

  • 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.