Neuroprotective effect of ebselen on rat hippocampal slices submitted to oxygen-glucose deprivation: correlation with immunocontent of inducible nitric oxide synthase

Neurosci Lett. 2003 Jul 31;346(1-2):101-4. doi: 10.1016/s0304-3940(03)00580-9.

Abstract

Ebselen is a seleno organic compound with antioxidant and anti-inflammatory properties, which is under clinical trials for the treatment of ischemic stroke. In this study, we attempted to correlate the protective effects of ebselen and the inducible nitric oxide synthase (iNOS) immunocontent in hippocampal slices submitted to oxygen-glucose deprivation (OGD), since the exacerbated production of nitric oxide by iNOS plays a role in the mechanisms of cellular death in ischemic insults. Ebselen (10 microM) protected slices from the deleterious effects of OGD (as assessed by MTT assay) only when present during all the recovery period (180 min). Moreover, ebselen added 5 and 15 min after the beginning of recovery only partially protected the slices from cellular death, while when added 30 min after the beginning of recovery no protection was observed. OGD increased the immunocontent of iNOS, and this increase was abolished also only when ebselen was present during all the recovery period. Our results indicate that the neuroprotective effect of ebselen could be related to this decrease in the iNOS immunocontent.

Publication types

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

MeSH terms

  • Animals
  • Azoles / pharmacology*
  • Azoles / therapeutic use
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Glucose / deficiency*
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Hippocampus / immunology
  • Isoindoles
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / immunology
  • Nitric Oxide Synthase Type II
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / therapeutic use
  • Rats
  • Rats, Wistar

Substances

  • Azoles
  • Isoindoles
  • Neuroprotective Agents
  • Organoselenium Compounds
  • ebselen
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Glucose