Antioxidants, but not cAMP or high K+, prevent arachidonic acid toxicity on neuronal cultures.
Arachidonic acid (AA) showed profound toxicity against primary neuronal cultures prepared from fetal rat striatum. This toxicity was attenuated by nordihydroguaiaretic acid but not by indomethacin, indicating that lipoxygenase pathway of AA metabolism is involved in the toxicity. Furthermore, the neurotoxic action of AA was abolished by antioxidants butylated hydroxyanisole or N-acetylcysteine. In contrast, treatment with forskolin or high K+, which have been shown to prevent neuronal death induced by MPP+ or high oxygen conditions, showed no protection against AA toxicity. These results suggest that, although oxygen free radicals generated through lipoxygenase metabolism is responsible for the neurotoxicity, distinct mechanisms from those of other oxidative stress are operative in AA-induced neuronal injury.
Katsuki
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Akino
N
N
Okuda
S
S
Saito
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D001095:Arachidonic Acids; D000242:Cyclic AMP; D011188:Potassium; D007213:Indomethacin