近年来,越来越多的证据表明氧化应激与许多遗传性代谢紊乱的病理生理学有关。然而,经典抗氧化剂在这些疾病中的临床应用评估不佳,到目前为止还没有证明任何益处。l-肉碱是内源性物质,其充当脂肪酸穿过随后的β-氧化和ATP产生所必需的线粒体内膜的载体。除了它在脂质代谢中的重要作用,l-肉碱也是一种有效的抗氧化剂(自由基清除剂),因此可以保护组织免受氧化损伤。这篇综述介绍了一些遗传性神经代谢疾病患者的最新发现,这些发现表明l-肉碱可能与减少这些疾病中观察到的氧化损伤有关。对于其中一些疾病,降低浓度的左旋肉碱可能发生由于该化合物的组合积累的有毒代谢物,尤其是有机酸,或由于蛋白质限制饮食。因此,补充左旋肉碱可能不仅有助于防止这种元素的组织缺陷,而且要避免这些疾病中反应性物种产生增加的继发性氧化损伤。考虑到左旋肉碱容易穿过血脑屏障的能力,补充l-肉碱还可以有益于预防由氧化损伤引起的神经损伤。然而,需要进一步的研究来更好地探索这种潜力。
In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.