Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration
Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration
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DOI：
10.1179/1351000215y.0000000026
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发表时间：
2016-01-01
期刊：
影响因子：
3.8
通讯作者：
Yoshino, Hiide
中科院分区：
文献类型：
--
作者：
Nagase, Midori;Yamamoto, Yorihiro;Yoshino, Hiide
目标和方法：与年龄匹配的健康对照组（n = 55）相比，肌萎缩侧索硬化（ALS）患者（n = 26）表现出增加的氧化应激，如通过氧化型辅酶Q10在总血浆辅酶Q10中的百分比（% CoQ 10）显著增加、血浆尿酸水平显著降低、以及多不饱和脂肪酸在总血浆游离脂肪酸（FFA）中的百分比显著降低。因此，疗效依达拉奉，一个自由基清除剂，在这些ALS patientsexamined.Results和讨论：在26例ALS患者中，17接受依达拉奉（30 mg/天，1至4次，每周）至少3个月，13个持续6个月。这些患者中修订的ALS功能评定量表（ALSFRS-R）的变化显著小于未接受依达拉奉治疗的ALS患者（n = 19）。与恶化组（.ALSFRS-R < -5）相比，在进展满意组（Δ ALSFRS-R >= 0）中，依达拉奉给药显著降低了血浆FFA水平和棕榈油酸和油酸含量（组织氧化损伤的血浆标志物）平均值的一个以上标准差的波动。依达拉奉治疗增加血浆尿酸，表明它是一种有效的过氧亚硝酸盐清除剂。然而，依达拉奉给药并未降低% CoQ 10。因此，与辅酶Q10等药物联合治疗可能会进一步降低ALS患者的氧化应激。
Objectives and methods: Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (% CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined.Results and discussion: Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (Delta ALSFRS-R >= 0) as compared to the ingravescent group (.ALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease % CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.