Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas.
Curr Neuropharmacol. 2010 Sep;8(3):194-210. doi: 10.2174/157015910792246236.
Toxins that pass through the blood-brain barrier put neurons and glia in peril. The damage inflicted is usually a consequence of the ability of these toxic agents to induce free radical generation within cells but especially at the level of the mitochondria. The elevated production of oxygen and nitrogen-based radicals and related non-radical products leads to the oxidation of essential macromolecules including lipids, proteins and DNA. The resultant damage is referred to as oxidative and nitrosative stress and, when the molecular destruction is sufficiently severe, it causes apoptosis or necrosis of neurons and glia. Loss of brain cells compromises the functions of the central nervous system expressed as motor, sensory and cognitive deficits and psychological alterations. In this survey we summarize the publications related to the following neurotoxins and the protective actions of melatonin: aminolevulinic acid, cyanide, domoic acid, kainic acid, metals, methamphetamine, polychlorinated biphenyls, rotenone, toluene and 6-hydroxydopamine. Given the potent direct free radical scavenging activities of melatonin and its metabolites, their ability to indirectly stimulate antioxidative enzymes and their efficacy in reducing electron leakage from mitochondria, it would be expected that these molecules would protect the brain from oxidative and nitrosative molecular mutilation. The studies summarized in this review indicate that this is indeed the case, an action that is obviously assisted by the fact that melatonin readily crosses the blood brain barrier.
通过血脑屏障的毒素使神经元和神经胶质处于危险之中。这种损伤通常是这些有毒物质在细胞内特别是在线粒体水平诱导自由基生成的能力的结果。氧和氮基自由基以及相关的非自由基产物的产生增加导致包括脂质、蛋白质和 DNA 在内的必需大分子的氧化。由此产生的损伤被称为氧化和硝化应激，当分子破坏足够严重时，它会导致神经元和神经胶质的细胞凋亡或坏死。脑细胞的丧失会损害中枢神经系统的功能，表现为运动、感觉和认知缺陷以及心理改变。在本综述中，我们总结了与以下神经毒素和褪黑素的保护作用有关的出版物：氨基酮戊酸、氰化物、软骨藻酸、海人藻酸、金属、甲基苯丙胺、多氯联苯、鱼藤酮、甲苯和 6-羟多巴胺。鉴于褪黑素及其代谢物具有强大的直接自由基清除活性，能够间接刺激抗氧化酶，并能有效减少线粒体电子泄漏，人们预计这些分子会保护大脑免受氧化和硝化分子损伤。本综述中总结的研究表明，情况确实如此，褪黑素很容易穿过血脑屏障，这显然有助于其发挥作用。
