UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion.
Neurosci Lett
; 561: 151-5, 2014 Feb 21.
Article
em En
| MEDLINE
| ID: mdl-24394910
ABSTRACT
Edaravone, an electron spin trapper with radical scavenging activity, has been shown to be effective in reducing infarct volume in humans following ischemic stroke. However, concerns of edaravone-induced renal toxicity have limited its clinical adoption. Previous work has demonstrated that edaravone produced significant neuroprotection when injected prior to a period of ischemia and/or reperfusion. The current investigation was designed to determine if a newly synthesized co-drug consisting of lipoic acid and edaravone, named UPEI-300, could produce neuroprotection in in vitro and/or an in vivo rodent model of stroke. UPEI-300 produced dose-dependent neuroprotection in vitro and was subsequently tested in vivo. Male rats were anaesthetized and the middle cerebral artery was occluded for 30 min followed by 5.5 h of reperfusion (ischemia/reperfusion; I/R). Pre-administration of UPEI-300 dose-dependently decreased infarct volume. Significant neuroprotection was also observed when UPEI-300 (1.0 mg/kg) was injected during the 30 min period of ischemia as well as up to 60 min following the start of reperfusion. These results indicate that a co-drug consisting of edaravone and lipoic acid is a potent neuroprotectant, and clinically, the use of such a novel co-drug following an ischemic stroke might maintain neuroprotection while potentially decreasing edaravone associated renal toxicity.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Isquemia Encefálica
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Antipirina
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Neuroglia
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Ácido Tióctico
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Fármacos Neuroprotetores
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Acidente Vascular Cerebral
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2014
Tipo de documento:
Article