Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: An in vivo microdialysis study
Edaravone inhibits lipid peroxidation in neonatal hypoxic-ischemic rats: An in vivo microdialysis study
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DOI：
10.1016/j.neulet.2006.10.024
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发表时间：
2007-02
影响因子：
2.5
通讯作者：
Jesmin I. Noor;Y. Ueda;T. Ikeda;T. Ikenoue
中科院分区：
文献类型：
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作者：
Jesmin I. Noor;Y. Ueda;T. Ikeda;T. Ikenoue
胎儿或新生儿早期发生的缺氧缺血会导致未成熟神经元的损伤，导致行为和心理功能障碍。自由基介导的脂质过氧化是包括新生儿脑损伤在内的神经毒性的主要原因。依达拉奉(3-甲基-1-苯基-2-吡唑啉-5-酮)是一种新型抗氧化剂，是治疗成人急性缺血性脑病的首选药物。本研究的目的是通过电子顺磁共振(EPR)和活体脑微透析的方法，观察依达拉奉对新生大鼠缺氧缺血性脑损伤时脂质过氧化产物的直接抑制作用。7日龄Wistar大鼠结扎左侧颈总动脉，在大鼠海马区插入探头。将依达拉奉(5、50或100μM)或生理盐水在低氧前、低氧期间和低氧后(8%O2暴露1h)分别注入自旋捕捉剂(α-(4-吡啶-N-氧化物)-N-叔丁基硝酮；POBN)，并进行电子顺磁共振分析。依达拉奉(100μM)在缺氧缺血期和缺氧缺血期后未显示任何POBN加合物形成的EPR证据。然而，与对照组相比，低氧组和依达拉奉50μM组的EPR信号增加，但在低氧期间并不明显。依达拉奉在5μM时显著增加EPR信号。本研究表明，依达拉奉可直接抑制新生大鼠缺氧缺血性脑损伤时产生的脂质自由基的形成，且呈剂量依赖关系。这些结果提示依达拉奉可通过抑制脂质自由基的形成来减轻新生大鼠脑内神经元的损伤。
The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions. Free radical-mediated lipid peroxidation is the main cause of neurotoxicity including neonatal brain damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel anti-oxidant agent and the drug of choice in the treatment of acute ischemic brain disorders in adult patient. The purpose of this study is to determine the direct effects of edaravone in inhibiting the lipid peroxidation production in the neonatal rat brains during hypoxic-ischemic insult by electron paramagnetic resonance (EPR) spectoroscopy and in vivo brain microdialysis. Seven-day-old Wistar rats were subjected to left common carotid artery ligation and a probe was inserted in the rat hippocampus. Edaravone (5, 50, or 100μM) or saline was perfused with a spin trap agent (α-(4-pyridyl-N-oxide)-N-tert-butylnitrone; POBN) before, during and after hypoxia (1h of 8% O2exposure) and then analyzed by EPR. Edaravone (100μM) did not show any EPR evidence of POBN adduct formation during and after hypoxic-ischemic insult. However, the EPR signal increased, but not significantly during the hypoxic period in the hypoxic and edaravone 50μM-treated groups compared to control. Edaravone at 5μM significantly increased the EPR signals compared to control. This study shows that edaravone directly and dose-dependently inhibited the formation of lipid free radicals produced during hypoxic-ischemic insult in the neonatal rat brain. These results suggest that edaravone is able to attenuate neuronal damage in the rat neonatal brain by inhibiting the formation of lipid radicals.