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耐药性部分性癫痫患者的氧化应激

Oxidative Stress in Patients with Drug Resistant Partial Complex Seizure.

作者信息

Lorigados Pedre Lourdes, Gallardo Juan M, Morales Chacón Lilia M, Vega García Angélica, Flores-Mendoza Monserrat, Neri-Gómez Teresa, Estupiñán Díaz Bárbara, Cruz-Xenes Rachel M, Pavón Fuentes Nancy, Orozco-Suárez Sandra

机构信息

Immunochemical Department, International Center for Neurological Restoration, 25th Ave, Playa, 15805 Havana, Cuba.

Medical Research Unit in Nephrological Diseases, Specialty Hospital, National Medical Center "XXI Century", IMSS, 06720 Mexico City, Mexico.

出版信息

Behav Sci (Basel). 2018 Jun 9;8(6):59. doi: 10.3390/bs8060059.

Abstract

Oxidative stress (OS) has been implicated as a pathophysiological mechanism of drug-resistant epilepsy, but little is known about the relationship between OS markers and clinical parameters, such as the number of drugs, age onset of seizure and frequency of seizures per month. The current study’s aim was to evaluate several oxidative stress markers and antioxidants in 18 drug-resistant partial complex seizure (DRPCS) patients compared to a control group (age and sex matched), and the results were related to clinical variables. We examined malondialdehyde (MDA), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), nitric oxide (NO), uric acid, superoxide dismutase (SOD), glutathione, vitamin C, 4-hydroxy-2-nonenal (4-HNE) and nitrotyrosine (3-NT). All markers except 4-HNE and 3-NT were studied by spectrophotometry. The expressions of 4-HNE and 3-NT were evaluated by Western blot analysis. MDA levels in patients were significantly increased ( ≤ 0.0001) while AOPP levels were similar to the control group. AGEs, NO and uric acid concentrations were significantly decreased ( ≤ 0.004, ≤ 0.005, ≤ 0.0001, respectively). Expressions of 3-NT and 4-HNE were increased ( ≤ 0.005) similarly to SOD activity ( = 0.0001), whereas vitamin C was considerably diminished ( = 0.0001). Glutathione levels were similar to the control group. There was a positive correlation between NO and MDA with the number of drugs. The expression of 3-NT was positively related with the frequency of seizures per month. There was a negative relationship between MDA and age at onset of seizures, as well as vitamin C with seizure frequency/month. We detected an imbalance in the redox state in patients with DRCPS, supporting oxidative stress as a relevant mechanism in this pathology. Thus, it is apparent that some oxidant and antioxidant parameters are closely linked with clinical variables.

摘要

氧化应激(OS)被认为是耐药性癫痫的一种病理生理机制,但关于OS标志物与临床参数之间的关系,如药物数量、癫痫发作起始年龄和每月癫痫发作频率等,人们了解甚少。本研究的目的是评估18例耐药性部分性复杂性发作(DRPCS)患者与对照组(年龄和性别匹配)的几种氧化应激标志物和抗氧化剂,并将结果与临床变量相关联。我们检测了丙二醛(MDA)、晚期氧化蛋白产物(AOPP)、晚期糖基化终末产物(AGEs)、一氧化氮(NO)、尿酸、超氧化物歧化酶(SOD)、谷胱甘肽、维生素C、4-羟基壬烯醛(4-HNE)和硝基酪氨酸(3-NT)。除4-HNE和3-NT外,所有标志物均采用分光光度法进行研究。4-HNE和3-NT的表达通过蛋白质免疫印迹分析进行评估。患者的MDA水平显著升高(≤0.0001),而AOPP水平与对照组相似。AGEs、NO和尿酸浓度显著降低(分别为≤0.004、≤0.005、≤0.0001)。3-NT和4-HNE的表达增加(≤0.005),与SOD活性相似(=0.0001),而维生素C显著减少(=0.0001)。谷胱甘肽水平与对照组相似。NO和MDA与药物数量呈正相关。3-NT的表达与每月癫痫发作频率呈正相关。MDA与癫痫发作起始年龄呈负相关,维生素C与每月癫痫发作频率也呈负相关。我们检测到DRCPS患者的氧化还原状态失衡,支持氧化应激是这种病理状态的相关机制。因此,很明显一些氧化和抗氧化参数与临床变量密切相关。

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