title: Antioxidant and neuroprotective properties of N-arachidonoyldopamine.
abstract: N-Acyldopamines were recently described as putative endogenous substances in the rat brain. Among them, N-arachidonoyldopamine (AADA) was characterized as cannabinoid CB1 and vanilloid TRPV1 receptor ligand. The physiological significance of such compounds is yet poorly understood. In this study, we describe the novel properties of AADA as antioxidant and neuroprotectant. Antioxidant potential of AADA and its analogs were first tested in the galvinoxyl assay. It was found that N-acyldopamines are potent antioxidants and that the number of free hydroxyl groups in the phenolic moiety of dopamine is essential for the activity. AADA dose dependently (0.1-10 microM) protected cultured cerebellar granule neurons (CGN) in the model of oxidative stress induced by hydrogen peroxide. N-Oleoyldopamine, another endogenous substance, was much less potent in these conditions while the natural antioxidant alpha-tocopherol was inactive. In this test, AADA decreased the peroxide level in CGN preparations and its neuroprotection was independent of cannabinoid/vanilloid receptors blockade. AADA (10 microM) also protected CGN from death induced by K(+)/serum deprivation and glutamate exitotoxicity. These data indicate that AADA may act as endogenous antioxidant in different pathological conditions.
authors: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. bobr@oxylipin.ibch.ru
authors: Mikhail Yu
authors: MY
authors: Bobrov
authors: Anatoly A
authors: AA
authors: Lizhin
authors: Ekaterina L
authors: EL
authors: Andrianova
authors: Natalia M
authors: NM
authors: Gretskaya
authors: Lidia E
authors: LE
authors: Frumkina
authors: Leonid G
authors: LG
authors: Khaspekov
authors: Vladimir V
authors: VV
authors: Bezuglov
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001681:Biological Assay; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D001095:Arachidonic Acids; D016895:Culture Media, Serum-Free; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010545:Peroxides; C474941:arachidonyl dopamine; D018698:Glutamic Acid; C488796:N-oleoyldopamine; D004298:Dopamine