Hamed Sherifa A, Nabeshima Toshitaka
Department of Neurology, Assiut University Hospital, Assiut, Egypt.
J Pharmacol Sci. 2005 Aug;98(4):340-53. doi: 10.1254/jphs.crj05003x. Epub 2005 Aug 2.
Neurologists have little concern about the high atherosclerotic risk among epileptics. Recent evidences mount that chronic epilepsy and prolonged use of antiepileptic drugs (AEDs) are associated with multiple risk factors that are critically implicated in pathobiology and dysfunction of the vessel wall through complex molecular mechanisms that promote atherogenesis. This review is concerned with three metabolic alterations, which are attributed as major risk factors for atherosclerosis among epileptics: altered metabolism of a) homocysteine (Hcy), b) lipids and lipoproteins, and c) uric acid. Most conventional AEDs reduce folic acid levels, thereby raising Hcy levels. Hyperhomosysteinemia is recently believed to induce endothelial dysfunction and promote atherosclerosis through complex oxidative and excitatory neurotoxic molecular mechanisms. However, Hcy itself is a convulsing substance with increased seizure recurrence and intractability to antiepileptic medications. AEDs can disturb lipid metabolism with resultant hypercholestrolemia and dyslipidemia, common recognized risks for atherosclerosis. Altered uric acid metabolism is common among epileptics. Uric acid has been implicated in endothelial cell damage and decreased endothelial nitric oxide bioavailability. In the presence of atherosclerotic milieu, uric acid interacts with other substrate toxicities and increased reactive oxygen species, accelerating atherosclerosis. The above information forms the rationale for future routine screening and correction of such metabolic alterations in epileptics. A convincing argument now develops that routine polyvitamin supplementation (folic acid, vitamin B12, vitamin B6, vitamin C, vitamin E, and beta-carotene) becomes increasingly important for women and men receiving AEDs at all ages. The atheroprotective effect of multivitamins is through their antioxidant and anti-inflammatory effects together with their lipid and Hcy lowering effects.
神经科医生对癫痫患者中高动脉粥样硬化风险关注较少。最近有越来越多的证据表明，慢性癫痫和长期使用抗癫痫药物（AEDs）与多种风险因素相关，这些因素通过促进动脉粥样硬化形成的复杂分子机制，在血管壁的病理生物学和功能障碍中起关键作用。本综述关注三种代谢改变，它们被认为是癫痫患者动脉粥样硬化的主要风险因素：a）同型半胱氨酸（Hcy）代谢改变、b）脂质和脂蛋白代谢改变、c）尿酸代谢改变。大多数传统抗癫痫药物会降低叶酸水平，从而提高Hcy水平。最近认为高同型半胱氨酸血症通过复杂的氧化和兴奋性神经毒性分子机制诱导内皮功能障碍并促进动脉粥样硬化。然而，Hcy本身是一种惊厥物质，会增加癫痫复发率并导致对抗癫痫药物难治。抗癫痫药物会干扰脂质代谢，导致高胆固醇血症和血脂异常，这是动脉粥样硬化公认的常见风险。尿酸代谢改变在癫痫患者中很常见。尿酸与内皮细胞损伤及内皮一氧化氮生物利用度降低有关。在存在动脉粥样硬化环境的情况下，尿酸与其他底物毒性相互作用并增加活性氧，加速动脉粥样硬化。上述信息构成了未来对癫痫患者此类代谢改变进行常规筛查和纠正的理论基础。现在有一个令人信服的观点，即常规补充多种维生素（叶酸、维生素B12、维生素B6、维生素C、维生素E和β-胡萝卜素）对所有年龄段接受抗癫痫药物治疗的男性和女性变得越来越重要。多种维生素的抗动脉粥样硬化作用是通过它们的抗氧化和抗炎作用以及它们降低脂质和Hcy的作用实现的。
