Neuroprotective effect of ebselen on rat hippocampal slices submitted to oxygen-glucose deprivation: correlation with immunocontent of inducible nitric oxide synthase.
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.
Porciúncula
Lisiane O
LO
Departamento de Bioqui;mica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - anexo, 90035-003, Porto Alegre, RS, Brazil. lopciuncula@yahoo.com
Rocha
João Batista T
JB
Cimarosti
Helena
H
Vinadé
Lúcia
L
Ghisleni
Gabriele
G
Salbego
Christianne G
CG
Souza
Diogo O
DO
D000818:Animals; D001393:Azoles / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D054833:Isoindoles; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D001393:Azoles; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C042986:ebselen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005947:Glucose