Effect of ebselen and organochalcogenides on excitotoxicity induced by glutamate in isolated chick retina

Brain Res. 2005 Mar 28;1039(1-2):146-52. doi: 10.1016/j.brainres.2005.01.062.

Abstract

In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca2+ influx into chick embryonic retinal cells, as well as their effects on the excitotoxic injury in retina cells. None of the compounds tested interfered with basal 45Ca2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca2+ influx. Diphenyl telluride (100-400 microM) decreased and ebselen (100-400 microM) completely blocked the glutamate-driven 45Ca2+ influx (P < 0.01) into chick retinal explants. The assessment of neural injury was made spectrophotometrically by quantification of cellularly reduced MTT (3(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 24 h after the beginning of glutamate exposure (8 h). Ebselen had no effects on retinal MTT reduction when co-incubated with glutamate for 8 h. However, when ebselen (100 and 400 microM) was co-incubated for 8 h with glutamate and remained in the incubation media until MTT evaluation (24 h after the beginning of incubation), it protected retinal cells against the decrease in MTT reduction induced by glutamate. These data indicate that besides its capacity of interacting with Ca2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoles / pharmacology*
  • Benzene Derivatives / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Chalcogens / pharmacology*
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • Glutamic Acid
  • Isoindoles
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / prevention & control
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins
  • Organometallic Compounds / pharmacology*
  • Organoselenium Compounds / pharmacology*
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Tellurium / pharmacology
  • Tetrazolium Salts / metabolism
  • Thiazoles / metabolism

Substances

  • Azoles
  • Benzene Derivatives
  • Calcium Channels
  • Chalcogens
  • Isoindoles
  • Neuroprotective Agents
  • Neurotoxins
  • Organometallic Compounds
  • Organoselenium Compounds
  • Tetrazolium Salts
  • Thiazoles
  • diphenyl telluride
  • diphenylditelluride
  • diphenyldiselenide
  • Glutamic Acid
  • ebselen
  • thiazolyl blue
  • Tellurium
  • Calcium