Haznedar Pınar, Doğan Özlem, Albayrak Pelin, Öz Tunçer Gökçen, Teber Serap, Deda Gülhis, Eminoglu F Tuba
Ankara University Faculty of Medicine, Department of Pediatrics Cebeci Mahallesi, Cebeci Yerleşkesi, 06590 Çankaya, Mamak, Ankara, Turkey.
Ankara University Faculty of Medicine, Biochemistry Cebeci Mahallesi, Cebeci Yerleşkesi, 06590 Çankaya, Mamak, Ankara, Turkey.
Epilepsy Res. 2019 Jul;153:7-13. doi: 10.1016/j.eplepsyres.2019.03.009. Epub 2019 Mar 15.
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.
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.
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.
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.
抗癫痫药物的使用与氧化损伤之间的关系尚未完全明确。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）及其相互关系。
在至少接受丙戊酸或左乙拉西坦治疗6个月的患者中，测定肝功能测试、血清游离肉碱和氧化损伤标志物及其相互关系。纳入25例接受治疗剂量丙戊酸的患者、26例接受治疗剂量左乙拉西坦的患者以及26名健康志愿者作为对照。测量肝功能测试、氨、肉碱、脂质过氧化生物标志物丙二醛（MDA）和DNA损伤敏感标志物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。数据采用IBM SPSS Statistics 22.0进行评估。
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。丙戊酸治疗的患者肉碱水平显著降低，然而未发现其与MDA、8-OHdG或肝功能测试相关。在左乙拉西坦组中，MDA与氨和8-OHdG呈正相关。
我们未观察到接受治疗剂量丙戊酸的患者出现肝毒性。然而，接受治疗剂量左乙拉西坦的癫痫儿童MDA和8-OHdG水平显著升高，这支持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。
