Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs
Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs
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DOI：
10.1016/j.seizure.2012.11.007
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发表时间：
2013-03-01
影响因子：
3
通讯作者：
Hasanoglu, Alev
中科院分区：
文献类型：
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作者：
Emeksiz, Hamdi Cihan;Serdaroglu, Ayse;Hasanoglu, Alev
目的：本研究旨在通过研究“高同型半胱氨酸血症(HHcy) ->不对称二甲基精氨酸（ADMA）增加->一氧化氮（NO）减少”的级联反应来评估儿童抗癫痫药物的动脉粥样硬化风险，该反应被认为有助于动脉粥样硬化的发展过程。方法：53例癫痫患者接受丙戊酸（VPA, n = 26）或奥卡西平（OXC, n = 27）治疗。24名性别和年龄匹配的健康儿童作为对照。测定空腹血浆总同型半胱氨酸（tHcy）、ADMA、NO水平。结果：VPA组、OXC组与对照组Hcy、ADMA、NO、维生素B-12、叶酸水平差异均不显著（p < 0.05）。在患者组（VPA组和OXC组）中，22.6%（12/53）的儿童tHcy水平高于正常临界值（13.1 mu mol/l）， 17%（9/53）的儿童tHcy水平高于15 mu mol/l，这是动脉粥样硬化风险增加的临界值（两者均p < 0.05）。VPA组与OXC组HHcy率差异无统计学意义（p < 0.05，均为HHcy临界值）。患者组tHcy水平与抗癫痫药物治疗时间呈正相关（r = +0.276, p < 0.05）。结论：使用OXC的患者可能发生HHcy。与以前的一些出版物相反，我们的数据并不表明OXC在HI-Icy风险方面比VPA更安全。进一步开展前瞻性、大规模和长期的研究，调查所有可能导致HHcy导致动脉粥样硬化的途径，以确定aed相关动脉粥样硬化的确切机制。(C) 2012年英国癫痫协会。Elsevier Ltd.出版。版权所有。
Purpose: The aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, "hyperhomocysteinemia (HHcy) -> asymmetric dimethylarginine (ADMA) increase -> nitric oxide (NO) decrease", which is thought to contribute to the developmental process of atherosclerosis.Methods: The participants included 53 epilepsy patients who received either valproic acid (VPA, n = 26) or oxcarbazepine (OXC, n = 27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.Results: The differences in Hcy, ADMA, NO, vitamin B-12 and folate levels between VPA, OXC and control groups were all insignificant (p > 0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1 mu mol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15 mu mol/l which is accepted as the critical value for an increased atherosclerosis risk (p < 0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p > 0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r = +0.276, p < 0.05).Conclusion: HHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HI-Icy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis. (C) 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.