Kabuto Hideaki, Amakawa Masao, Mankura Mitsumasa, Yamanushi Tomoko T, Mori Akitane
Department of Health Sciences, Kagawa Prefectural College of Health Sciences, 281-1, Mure-Cho, Takamatsu, 761-0123, Japan.
Neurochem Res. 2009 Jul;34(7):1299-303. doi: 10.1007/s11064-008-9909-0. Epub 2009 Feb 15.
Superoxide and hydroxyl radicals are implicated in the pathogenesis of Parkinson disease, and induction of lipid peroxidation is an important factor in progression of this disease. Docosahexaenoic acid (DHA) is a key component of the cell membrane, and its peroxidation is inducible due to the double-bond chemical structure. However, DHA has neuroprotective effects. In this study, we examined the effects of intraperitoneal injection (ipi) of DHA ethyl ester (DHA-Et) on 6-hydroxydopamine (6-OHDA)-induced dopamine (DA) reduction in the mouse striatum. DHA-Et ipi for 7 days before and 7 days after a single intracerebroventricular injection of 6-OHDA enhanced 6-OHDA-induced reduction of striatal DA level. On the other hand, ipi of DHA-Et for 7 days increased its concentration in the striatum. Co-injection of DHA-Et and 6-OHDA increased the levels of thiobarbituric acid-reactive substances (a marker of lipid peroxidation) in the striatum. Our results suggest that DHA-Et enhances 6-OHDA-induced DA depression by increasing lipid peroxidation, and that excessive use of DHA-Et may increase the susceptibility of Parkinson disease in animal model.
超氧阴离子和羟基自由基与帕金森病的发病机制有关，脂质过氧化的诱导是该疾病进展的一个重要因素。二十二碳六烯酸（DHA）是细胞膜的关键成分，由于其双键化学结构，其过氧化是可诱导的。然而，DHA具有神经保护作用。在本研究中，我们检测了腹腔注射（ipi）DHA乙酯（DHA-Et）对6-羟基多巴胺（6-OHDA）诱导的小鼠纹状体多巴胺（DA）减少的影响。在单次脑室内注射6-OHDA之前和之后7天进行7天的DHA-Et ipi增强了6-OHDA诱导的纹状体DA水平降低。另一方面，7天的DHA-Et ipi增加了其在纹状体中的浓度。DHA-Et与6-OHDA共同注射增加了纹状体中硫代巴比妥酸反应性物质（脂质过氧化的标志物）的水平。我们的结果表明，DHA-Et通过增加脂质过氧化增强了6-OHDA诱导的DA抑制，并且过量使用DHA-Et可能会增加动物模型中帕金森病的易感性。
