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.
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