Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.
Int J Mol Sci. 2023 Feb 15;24(4):3873. doi: 10.3390/ijms24043873.
Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a "U-shaped" dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.
癫痫是一种中枢神经系统的慢性疾病，其特征是反复发作的癫痫发作。由于癫痫发作或癫痫持续状态下氧化剂过度形成，这可能是神经元死亡的原因之一。鉴于氧化应激在癫痫发生中的作用，以及该过程在其他神经疾病中的参与，我们决定回顾关于选定的新型抗癫痫药物（AEDs），也称为抗癫痫药物，与氧化应激之间关系的最新知识状态。文献综述表明，增强 GABA 能传递的药物（例如，氨己烯酸、噻加宾、加巴喷丁、托吡酯）或其他抗癫痫药（例如，拉莫三嗪、左乙拉西坦）可降低神经元氧化标志物。特别是，左乙拉西坦在这方面可能产生模棱两可的效果。然而，当将增强 GABA 的药物应用于健康组织时，它往往会以剂量依赖性方式增加氧化应激标志物。关于地西泮的研究表明，它在兴奋性毒性或氧化应激后以“U 形”剂量依赖性方式发挥神经保护作用。其较低的浓度不足以防止神经元损伤，而较高的浓度则产生神经退行性变。因此，可以得出结论，增强 GABA 能神经传递的新型 AED 可能与地西泮类似，在高剂量使用时会导致神经退行性变和氧化应激。
