Laboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, Moscow, 125367, Russia; Faculty of Ecology, Peoples' Friendship University of Russia, Moscow, 117198, Russia.
Laboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, Moscow, 125367, Russia; Faculty of Biology, Moscow State University, Moscow, 119234, Russia.
Regul Toxicol Pharmacol. 2018 Jun;95:254-259. doi: 10.1016/j.yrtph.2018.03.025. Epub 2018 Mar 28.
In a model of early-stage Parkinson's disease induced by a single intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Wistar rats, a neuroprotective effect of a new derivative of carnosine and α-lipoic acid (C/LA nanomicellar complex) was demonstrated. Acute intraperitoneal administration of carnosine, α-lipoic acid and C/LA complex following MPTP administration normalized the total antioxidant activity in the brain tissue. Of all the compounds tested only C/LA complex normalized the metabolism of dopamine (DA) and serotonin (5-HT), while its components did not show similar effects when used separately. C/LA complex effectively restored the level of DA metabolites: the level of DOPAC was increased by 24.7 ± 5.6% compared to the animals that had received MPTP only, and the level of HVA was restored to the values observed in the intact animals. Integral metabolic indices of DA (DOPAC/DA and HVA/DA ratios) and 5-HT turnover (5-HIAA/5-HT ratio) in the striatum tended to increase in case of C/LA complex administration.
在通过单次鼻腔内给予 Wistar 大鼠 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的早期帕金森病模型中，展示了肉毒碱和 α-硫辛酸（C/LA 胶束复合物）的新衍生物的神经保护作用。MPTP 给药后，急性腹腔内给予肉毒碱、α-硫辛酸和 C/LA 复合物可使脑组织中的总抗氧化活性正常化。在所测试的所有化合物中，只有 C/LA 复合物可使多巴胺（DA）和 5-羟色胺（5-HT）的代谢正常化，而其成分单独使用时则没有类似的作用。C/LA 复合物可有效恢复 DA 代谢物的水平：与仅接受 MPTP 的动物相比，DOPAC 的水平增加了 24.7±5.6%，而 HVA 的水平则恢复到完整动物观察到的水平。纹状体中 DA（DOPAC/DA 和 HVA/DA 比值）和 5-HT 周转率（5-HIAA/5-HT 比值）的综合代谢指数在给予 C/LA 复合物的情况下趋于增加。
