Neuroprotective effects of a new glutathione peroxidase mimetic on neurons of the chick embryo's retina.
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.
Castagné
V
V
Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Lausanne, Switzerland. vincent.castagne@inst.hospvd.ch
Clarke
P G
PG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019771:Axotomy; D001393:Azoles / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D001393:Azoles; D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D016566:Organoselenium Compounds; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C114695:BXT 51072; D016202:N-Methylaspartate; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase