Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury
Alkoxyl radical-scavenging activity of edaravone in patients with traumatic brain injury
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DOI：
10.1089/neu.2006.23.1591
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Arugai, Tohru
中科院分区：
文献类型：
--
作者：
Dohi, Kenji;Satoh, Kazue;Arugai, Tohru
脂质过氧化是由活性氧（ROS）引起的，与创伤性脑损伤（TBI）有关。因此，TBI的治疗策略可能是控制脂质过氧化。迄今为止，唯一被批准用于阻断脂质过氧化的药物是依达拉奉（MCI-186），这是一种新型自由基清除剂，在急性缺血性中风中发挥神经保护作用。虽然依达拉曲能清除羟基和一氧化氮自由基，但其对烷氧基自由基（OR-）的影响尚不清楚，而烷氧基自由基也有助于脂质过氧化。迄今为止，血液中自由基的研究受到检测技术困难的严重阻碍。我们采用体外和离体电子自旋共振（ESR）方法，以5,5-二甲基吡咯- n -氧化物为自旋阱，研究依达拉屈酮是否具有清除OR-的作用。通过将高铁血红蛋白或人血与过氧化叔丁基混合，我们发现该技术可以检测体外生成的or。我们还发现，体外给药400 μ M依达拉奉可以完全吸收产生的OR-。对17例TBI患者在给予依达拉奉（30mg，静脉注射）之前和之后20分钟采集的颈静脉血进行分析，发现未经治疗的患者血液中的OR-水平高于正常对照血液样本。然而，依达拉奉治疗可抑制这些OR-水平24.6%（自由基强度= 71.1 +/- 5.2-53.6 +/- 5.2;p < 0.01）。因此，依达拉奉可以清除OR-并显著降低这些自由基在TBI患者中的水平。本文描述的新型离体ESR方法提供了一种有价值的氧化应激临床测量方法。
Lipid peroxidation is caused by reactive oxygen species (ROS) and is involved in traumatic brain injury (TBI). Consequently, a therapeutic strategy for TBI may be to control lipid peroxidation. The only drug approved to date for blocking lipid peroxidation is edaravone (MCI-186), a novel free-radical scavenger shown to exert neuroprotective effects in acute ischemic stroke. Although edaravone scavenges hydroxyl and nitric oxide radicals, its effect on alkoxyl radicals (OR-), which also contribute to lipid peroxidation, is unknown. To date, the study of free radicals in blood has been severely hampered by technical difficulties in their detection. We used an in vitro and ex vivo electron spin resonance (ESR) method employing 5,5-dimethyl-l-pyrroline-N-oxide as a spin trap to investigate whether edaravone can scavenge OR-. By mixing either methemoglobin or human blood with tert-butyl hydroperoxide, we found that this technique can detect OR- generated in vitro. We also found that generated OR- can be completely absorbed by administration of edaravone in vitro (400 mu M). Analysis of jugular venous blood collected from 17 TBI patients immediately before and 20 minutes after the administration of edaravone (30 mg, i.v.) revealed higher OR- levels in the untreated patients blood than in normal control blood samples. However, treatment with edaravone suppressed these OR- levels by 24.6% (radical intensity = 71.1 +/- 5.2-53.6 +/- 5.2; p < 0.01). Thus, edaravone can scavenge OR- and significantly reduce levels of these radicals in TBI patients. The novel ex vivo ESR method described here provides a valuable clinical measure of oxidative stress.