UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion
UPEI-300, a conjugate of lipoic acid and edaravone, mediates neuroprotection in ischemia/reperfusion
复制标题
DOI：
10.1016/j.neulet.2013.12.060
复制
发表时间：
2014-02-21
影响因子：
2.5
通讯作者：
Saleh, Tarek M.
中科院分区：
文献类型：
--
作者：
Connell, Barry J.;Saleh, Monique C.;Saleh, Tarek M.
依达拉奉是一种具有自由基清除活性的电子自旋捕获剂，已被证明可有效减少缺血性卒中后人类的梗死体积。然而，对依达拉奉诱导的肾毒性的担忧限制了其临床应用。先前的工作已经证明，依达拉奉在缺血和/或再灌注一段时间之前注射时产生显著的神经保护作用。目前的研究旨在确定一种新合成的由硫辛酸和依达拉奉组成的联合药物，命名为UPEI-300，是否可以在体外和/或体内啮齿动物中风模型中产生神经保护作用。UPEI-300在体外产生剂量依赖性神经保护作用，随后在体内进行测试。将雄性大鼠麻醉，将大脑中动脉闭塞30分钟，然后再灌注5.5小时（缺血/再灌注; I/R）。预先给予UPEI-300剂量依赖性地减少梗死体积。当在缺血30 min期间以及再灌注开始后60 min内注射UPEI-300（1.0 mg/kg）时，也观察到显著的神经保护作用。这些结果表明，由依达拉奉和硫辛酸组成的联合药物是一种有效的神经保护剂，临床上，缺血性卒中后使用这种新型联合药物可能维持神经保护，同时可能降低依达拉奉相关的肾毒性。(C)2014爱思唯尔爱尔兰有限公司版权所有。
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 mm 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.