Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
Department of Neurology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia.
Medicina (Kaunas). 2024 Aug 12;60(8):1299. doi: 10.3390/medicina60081299.
Oxidative stress resulting from a disturbance of the endogenous redox system is suspected in numerous diseases of the central nervous system, including epilepsy. In addition, antiseizure medications (ASMs), especially those of the old generation, may further increase oxidative stress. To evaluate the effects of ASM generation on oxidative stress, we conducted a cross-sectional study in patients with epilepsy treated with old, new, and polytherapy. : The antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, as well as the concentrations of malondialdehyde, protein carbonyl, nitrate, nitrite, and glutathione in reduced and oxidized forms, were measured in 49 patients with epilepsy and 14 healthy controls. In addition, the plasma concentrations of ASMs and metabolites of carbamazepine and valproic acid were measured in the patients. : Patients with epilepsy showed increased activities of superoxide dismutase and catalase ( < 0.001), concentrations of glutathione disulfide and markers of nitric oxide metabolism ( < 0.001), and decreased activities of glutathione peroxidase, glutathione reductase, glutathione, and nitrite concentrations ( ≤ 0.005) compared to healthy controls. A comparison of ASM generations revealed increased levels of superoxide dismutase and catalase ( ≤ 0.007) and decreased levels of glutathione peroxidase and glutathione reductase ( ≤ 0.01) in patients treated with old ASMs compared to those treated with new generation ASMs. In addition, an increase in protein carbonyl and nitric oxide metabolites ( ≤ 0.002) was observed in patients treated with old generation ASMs compared to those treated with new generation ASMs. Most oxidative stress parameters in patients receiving polytherapy with ASMs were intermediate between the results of patients treated with the old and new generations of ASMs. : An increase in oxidative stress markers and modulation of antioxidant enzyme activities was observed in patients with epilepsy compared to controls. The results of our study showed significantly higher oxidative stress in patients treated with old ASMs compared to those treated with new generation ASMs.
氧化应激是由于内源性氧化还原系统紊乱引起的，在中枢神经系统的许多疾病中都有嫌疑，包括癫痫。此外，抗癫痫药物（ASM），特别是旧一代的药物，可能会进一步增加氧化应激。为了评估 ASM 代际对氧化应激的影响，我们对接受旧、新和多药治疗的癫痫患者进行了横断面研究。方法：我们在 49 名癫痫患者和 14 名健康对照者中测量了超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶的抗氧化活性，以及丙二醛、蛋白羰基、硝酸盐、亚硝酸盐和还原型和氧化型谷胱甘肽的浓度。此外，我们还在患者中测量了 ASM 及其卡马西平和丙戊酸代谢物的血浆浓度。结果：与健康对照组相比，癫痫患者的超氧化物歧化酶和过氧化氢酶活性增加（＜0.001），谷胱甘肽二硫化物和一氧化氮代谢标志物浓度增加（＜0.001），谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽和亚硝酸盐浓度降低（≤0.005）。与新代 ASM 治疗组相比，旧代 ASM 治疗组患者的超氧化物歧化酶和过氧化氢酶水平升高（≤0.007），谷胱甘肽过氧化物酶和谷胱甘肽还原酶水平降低（≤0.01）。此外，与新代 ASM 治疗组相比，旧代 ASM 治疗组患者的蛋白羰基和一氧化氮代谢物增加（≤0.002）。接受 ASM 多药治疗的患者的大多数氧化应激参数在旧代和新代 ASM 治疗患者之间的结果之间处于中间位置。结论：与对照组相比，癫痫患者的氧化应激标志物增加，抗氧化酶活性发生调节。我们的研究结果表明，与新代 ASM 治疗组相比，旧代 ASM 治疗组患者的氧化应激显著更高。
