Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies
Effects of levetiracetam and valproic acid treatment on liver function tests, plasma free carnitine and lipid peroxidation in childhood epilepsies
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DOI：
10.1016/j.eplepsyres.2019.03.009
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发表时间：
2019-07-01
影响因子：
2.2
通讯作者：
Eminoglu, F. Tuba
中科院分区：
文献类型：
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作者：
Haznedar, Pinar;Dogan, Ozlem;Eminoglu, F. Tuba
背景和目的：抗癫痫药物的使用与氧化损伤之间的关系尚未明确。在我们的研究中，我们调查了接受丙戊酸或左乙拉西坦治疗的癫痫儿童的氧化应激参数、肉碱水平、肝功能测试（LFT）及其关系。在接受丙戊酸或左乙拉西坦治疗至少 6 个月的患者中测定了 LFT、血清游离肉碱和氧化损伤标志物及其相互关系。包括 25 名接受治疗剂量丙戊酸的患者、26 名接受治疗剂量左乙拉西坦的患者和 26 名健康志愿者作为对照。测量了 LFT、氨、肉碱、脂质过氧化生物标志物丙二醛 (MDA) 和 DNA 损伤的敏感标志物 8-羟基-2-脱氧鸟苷 (8-OHdG) 水平。将患者的结果与健康对照进行比较。使用 IBM SPSS Statistics 22.0 评估数据。结果：使用左乙拉西坦的患者氨和 MDA 水平升高；两组患者的 8-OHdG 水平均升高。丙戊酸治疗患者的肉毒碱水平明显较低，但未发现其与 MDA、8-OHdG 或 LFT 相关。左乙拉西坦组MDA与氨和8-OHdG呈正相关。结论：在治疗剂量的丙戊酸治疗下，我们没有观察到患者出现肝毒性。然而，接受左乙拉西坦治疗剂量的癫痫儿童的 MDA 和 8-OHdG 水平显着升高，这支持了左乙拉西坦治疗下的氧化损伤。这一结果首次在儿童癫痫中观察到，需要进一步研究以了解其机制。
Background and aims: The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam.Method. LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured.Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0. Results: Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group.Conclusion: We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.