Oxidant-antioxidant imbalance in the erythrocytes of sporadic amyotrophic lateral sclerosis patients correlates with the progression of disease

Oxidant-antioxidant imbalance in the erythrocytes of sporadic amyotrophic lateral sclerosis patients correlates with the progression of disease
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DOI:
10.1016/j.neuint.2008.01.009
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发表时间:
2008-05-01
影响因子:
4.2
通讯作者:
Misra, U. K.
Misra, U. K.
中科院分区:
医学3区
文献类型:
--
作者:
Babu, G. Nagesh;Kumar, Alok;Misra, U. K.

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自由基与许多疾病过程有关,包括运动神经元变性(MND)。抗氧化防御酶:红细胞中的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSHPx)、谷胱甘肽还原酶(GR)和葡萄糖-6-磷酸脱氢酶(G-6-PDH)能够对内源性或外源性产生的活性氧进行解毒。本研究对20例散发性肌萎缩侧索硬化(ALS)患者和20例正常人红细胞脂质过氧化(LPO)和抗氧化防御功能进行了检测,发现ALS患者红细胞脂质过氧化水平明显高于正常人(P < 0.001)。过氧化氢酶活性显著降低(P < 0.001)。ALS患者的葡萄糖-6-磷酸脱氢酶、谷胱甘肽还原酶活性和谷胱甘肽水平也明显低于健康人(P < 0.001、P < 0.01和P < 0.01)。进一步观察到,随着肌萎缩侧索硬化症从6个月进展到24个月,脂质过氧化开始增加,过氧化氢酶、谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶活性和谷胱甘肽水平开始降低,表明这些参数与肌萎缩侧索硬化症的持续时间相关。这项研究证实了氧化应激参与肌萎缩侧索硬化症的进展和需要开发特定的外周生物标志物。(C)2008爱思唯尔有限公司保留所有权利。
Free radicals are implicated in numerous disease processes including motor neuron degeneration (MND). Antioxidant defense enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G-6-PDH) in the erythrocytes are capable of detoxifying reactive oxygen species produced endogenously or exogenously. In the present study, the extent of lipid peroxidation (LPO) and antioxidant defenses were evaluated in the erythrocytes of 20 sporadic amyotrophic lateral sclerosis (ALS) patients and 20 controls.We observed that lipid peroxidation in the erythrocytes of amyotrophic lateral sclerosis patients significantly increased with respect to controls (P < 0.001). On the other hand, catalase activity was found to be significantly lower (P < 0.001). The activities of glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione levels were also found to be significantly reduced in ALS patients compared to healthy subjects (P < 0.001, P < 0.01 and P < 0.01, respectively). It was further observed that lipid peroxidation started to increase and catalase, glutathione reductase, glucose-6-phosphate dehydrogenase enzyme activities and glutathione levels started to decrease as amyotrophic lateral sclerosis progressed from 6 to 24 months, suggesting a correlation between these parameters and duration of amyotrophic lateral sclerosis. This study confirms the involvement of oxidative stress during the progression of amyotrophic lateral sclerosis and the need to develop specific peripheral biomarkers. (C) 2008 Elsevier Ltd. All rights reserved.