UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion.

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.

• Authors: Barry J Connell, Monique C Saleh, Inan Kucukkaya, Alaa S Abd-El-Aziz, Bobby V Khan, Tarek M Saleh
• Journal: Neuroscience letters (Neurosci Lett) Vol. 561 Pg. 151-5 (Feb 21 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24394910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Drug Combinations
• Neuroprotective Agents
• UPEI-300
• Thioctic Acid
• Antipyrine

Topics

• Animals
• Antipyrine (analogs & derivatives, pharmacology, therapeutic use)
• Brain Ischemia (pathology, prevention & control)
• Cell Hypoxia
• Cells, Cultured
• Drug Combinations
• Male
• Neocortex (cytology)
• Neuroglia (drug effects, pathology)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats, Sprague-Dawley
• Reperfusion Injury (pathology, prevention & control)
• Stroke (pathology, prevention & control)
• Thioctic Acid (analogs & derivatives, pharmacology, therapeutic use)