title: Docosahexaenoic acid ethyl ester enhances 6-hydroxydopamine-induced neuronal damage by induction of lipid peroxidation in mouse striatum.
abstract: 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.
authors.affiliation: Department of Health Sciences, Kagawa Prefectural College of Health Sciences, 281-1, Mure-Cho, Takamatsu, 761-0123, Japan. kabuto@chs.pref.kagawa.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kabuto
authors.forename: Masao
authors.initials: M
authors.lastname: Amakawa
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Mankura
authors.forename: Tomoko T
authors.initials: TT
authors.lastname: Yamanushi
authors.forename: Akitane
authors.initials: A
authors.lastname: Mori
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017392:Thiobarbituric Acid Reactive Substances; D015102:3,4-Dihydroxyphenylacetic Acid; D004281:Docosahexaenoic Acids; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid