Antioxidant and neuroprotective properties of N-arachidonoyldopamine.
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.
Bobrov
Mikhail Yu
MY
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. bobr@oxylipin.ibch.ru
Lizhin
Anatoly A
AA
Andrianova
Ekaterina L
EL
Gretskaya
Natalia M
NM
Frumkina
Lidia E
LE
Khaspekov
Leonid G
LG
Bezuglov
Vladimir V
VV
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
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