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癫痫女性的氧化应激增加:这是抗癫痫药物致畸作用的潜在机制吗?

Oxidative stress is increased in women with epilepsy: Is it a potential mechanism of anti-epileptic drug-induced teratogenesis?

作者信息

Deepa Damayanthi, Jayakumari Narayani, Thomas Sanjeev V

机构信息

Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.

出版信息

Ann Indian Acad Neurol. 2012 Oct;15(4):281-6. doi: 10.4103/0972-2327.104336.

DOI:10.4103/0972-2327.104336
PMID:23349593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3548366/
Abstract

CONTEXT

Oxidative stress can be a final common pathway for AED-induced teratogenesis.

AIMS

To compare the oxidative stress of women with epilepsy (WWE) and unfavorable pregnancy outcome (fetal malformation or spontaneous abortion - group EM) with that of WWE with normal pregnancy outcome (group ENM) and healthy women with normal pregnancy outcome (group C).

MATERIALS AND METHODS

We identified WWE under group EM (n = 43) and group ENM (n = 22) from the Kerala Registry of Epilepsy and Pregnancy (KREP). Group C was constituted of healthy volunteers (N = 20). Oxidative stress was assessed by estimating serum levels of malondialdehyde (MDA) and isoprostane (ISP). The antioxidant profile was evaluated as activity of superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT), total antioxidant status (TAO), and glutathione (GSH) content.

RESULTS

The MDA and ISP levels for group EM (3.46 + 0.82 and 17.77 + 3.0) were higher than that of group ENM (3.07 + 1.02 and 14.0 + 5.3), and both were significantly higher than that of group C (2.42 + 0.51 and 10.77 + 4.1). Their levels of SOD (146.82 + 42.64 vs. 175.81 + 42.61) and GSH (0.98 + 0.98 vs. 1.55 + 1.3) were significantly lower than those of controls. No significant changes were seen in TAO and GR. WWE on polytherapy showed significant increase in MDA when compared to monotherapy group.

CONCLUSION

WWE (group EM and ENM) had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with unfavorable pregnancy outcome (group EM) had higher oxidative stress. Excess oxidative stress can be a final common pathway, by which AEDs exert teratogenic effects.

摘要

背景

氧化应激可能是抗癫痫药物(AED)诱导致畸作用的最终共同途径。

目的

比较癫痫女性(WWE)中妊娠结局不良(胎儿畸形或自然流产——EM组)与妊娠结局正常的WWE(ENM组)以及妊娠结局正常的健康女性(C组)的氧化应激情况。

材料与方法

我们从喀拉拉邦癫痫与妊娠登记处(KREP)中确定了EM组(n = 43)和ENM组(n = 22)的WWE。C组由健康志愿者组成(N = 20)。通过估算血清丙二醛(MDA)和异前列腺素(ISP)水平评估氧化应激。抗氧化指标通过超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GR)、过氧化氢酶(CAT)活性、总抗氧化状态(TAO)以及谷胱甘肽(GSH)含量进行评估。

结果

EM组的MDA和ISP水平(3.46 + 0.82和17.77 + 3.0)高于ENM组(3.07 + 1.02和14.0 + 5.3),且两者均显著高于C组(2.42 + 0.51和10.77 + 4.1)。他们的SOD(146.82 + 42.64对175.81 + 42.61)和GSH(0.98 + 0.98对1.55 + 1.3)水平显著低于对照组。TAO和GR未见显著变化。与单药治疗组相比,联合治疗的WWE的MDA显著升高。

结论

WWE(EM组和ENM组)具有更高的氧化应激和更低的抗氧化活性。妊娠结局不良的WWE亚组(EM组)具有更高的氧化应激。过量的氧化应激可能是AED发挥致畸作用的最终共同途径。

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