Prasad D K V, Satyanarayana U, Shaheen Uzma, Prabha T Surya, Munshi Anjana
Assistant Professor, Department of Biochemistry, NRI Institute of Medical Sciences, Visakhapatnam, Andhra Pradesh, India.
Professor, Department of Biochemistry, Dr Pinnamaneni Institute of Medical Sciences, Gannavaram, Andhra Pradesh, India.
J Clin Diagn Res. 2017 Sep;11(9):BC05-BC08. doi: 10.7860/JCDR/2017/29133.10604. Epub 2017 Sep 1.
Oxidative stress resulting from excessive generation of Reactive Oxygen Species (ROS) plays a significant role in neurodegeneration associated with seizures/epilepsy.
To evaluate oxidative stress markers and antioxidant enzymes in Genetic Generalised Epilepsy (GGE) and to know the extent of oxidative stress induced by Anti-Epileptic Drugs (AEDs) with the time duration of treatment.
In this case-control study, 310 GGE patients (male:female=203:107), who were on AED treatment (n=235) and 75 untreated patients (male:female=49:26) along with 310 age and sex matched healthy controls were recruited. Oxidative stress markers such as Nitric Oxide (NO), Malondialdehyde (MDA) and antioxidant enzyme activities namely Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT) were measured spectrophotometrically.
Significantly higher levels of serum NO, MDA and low levels of plasma Total Antioxidant Capacity (TAC) were found in patients as compared to controls (p<0.001) whereas erythrocyte SOD, CAT and GPx activities were found to be significantly low in patients when compared to the control group (p<0.001). Statistically significant higher levels of NO, MDA and lower levels of SOD, CAT and TAC were observed in patients subgroup, who were on AEDs for more than >5 years compared to other groups (≤ 1 year and 1-≤ 5 years) (p=0.02, p=0.01, p=0.001, p=0.01 and p=0.05 respectively). Further, significant increase in the levels of NO, MDA and decreased activities of SOD, CAT were found in treated patients compared to untreated patients (p<0.05) denoting that additional oxidative stress induced by AEDs which results in seizure recurrence and drug intractability.
Our study demonstrated that GGE patients have additional oxidative stress due to AEDs and decreased antioxidant enzyme activities causing an imbalance between oxidant and antioxidant status, which might contribute to the pathogenesis of GGE.
活性氧（ROS）过量生成导致的氧化应激在与癫痫发作/癫痫相关的神经退行性变中起重要作用。
评估遗传性全身性癫痫（GGE）中的氧化应激标志物和抗氧化酶，并了解抗癫痫药物（AEDs）随治疗时间诱导的氧化应激程度。
在这项病例对照研究中，招募了310例接受AED治疗的GGE患者（男∶女 = 203∶107）（n = 235）和75例未治疗患者（男∶女 = 49∶26），以及310例年龄和性别匹配的健康对照。采用分光光度法测定氧化应激标志物如一氧化氮（NO）、丙二醛（MDA）以及抗氧化酶活性，即超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）。
与对照组相比，患者血清中NO、MDA水平显著升高，血浆总抗氧化能力（TAC）水平降低（p < 0.001）；而与对照组相比，患者红细胞SOD、CAT和GPx活性显著降低（p < 0.001）。与其他组（≤1年和1至≤5年）相比，接受AEDs治疗超过5年的患者亚组中，NO、MDA水平在统计学上显著更高，SOD、CAT和TAC水平更低（分别为p = 0.02、p = 0.01、p = 0.001、p = 0.01和p = 0.05）。此外，与未治疗患者相比，治疗患者的NO、MDA水平显著升高，SOD、CAT活性降低（p < 0.05），表明AEDs诱导了额外的氧化应激，导致癫痫复发和药物难治性。
我们的研究表明，GGE患者因AEDs存在额外的氧化应激，抗氧化酶活性降低，导致氧化剂和抗氧化剂状态失衡，这可能有助于GGE的发病机制。
