Neuroprotective effects of a new glutathione peroxidase mimetic on neurons of the chick embryo's retina

J Neurosci Res. 2000 Feb 15;59(4):497-503. doi: 10.1002/(SICI)1097-4547(20000215)59:4<497::AID-JNR4>3.0.CO;2-B.

Abstract

During their period of naturally occurring neuronal death, retinal ganglion cells are particularly vulnerable to axotomy. The resulting cell death requires protein synthesis and is redox-regulated, since antioxidants protect axotomized-ganglion cells when given in doses that maintain the redox status near an optimal set-point. Here we report the effects of BXT-51072, a new glutathione peroxidase mimetic, on ganglion cell death induced in various ways in the retinas of chick embryos. The intraocular injection of BXT-51072 protected axotomized neurons at doses in a narrow (tenfold) range. It also reduced the deleterious effects of intraocular tert-butyl hydroperoxide, an inducer of lipid peroxidation, and diminished the excitotoxic degeneration induced by N-methyl-D-aspartate. However, BXT-51072 did not noticeably reduce naturally occurring cell death. Globally, our results show that BXT-51072 has numerous protective effects in the retina. In accordance with published data, the present report indicates that glutathione peroxidase mimetics may have potential applications for neurologic or degenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Axotomy
  • Azoles / pharmacology*
  • Cell Count / drug effects
  • Cell Death / drug effects
  • Cell Death / physiology
  • Chick Embryo
  • Excitatory Amino Acid Agonists / pharmacology
  • Free Radical Scavengers / pharmacology
  • Glutathione Peroxidase / metabolism
  • Metalloporphyrins / pharmacology
  • N-Methylaspartate / pharmacology
  • Organoselenium Compounds / pharmacology*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / physiology
  • tert-Butylhydroperoxide / pharmacology

Substances

  • Antioxidants
  • Azoles
  • Excitatory Amino Acid Agonists
  • Free Radical Scavengers
  • Metalloporphyrins
  • Organoselenium Compounds
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • BXT 51072
  • N-Methylaspartate
  • tert-Butylhydroperoxide
  • Glutathione Peroxidase