ANTIOXIDANTS, BUT NOT CAMP OR HIGH K-ACID TOXICITY ON NEURONAL CULTURES(, PREVENT ARACHIDONIC)

ARACHIDONIC acid (AA) showed profound toxicity against primary neurona l cultures prepared from fetal rat striatum. This toxicity was attenua ted by nordihydroguaiaretic acid but not by indomethacin, indicating t hat lipoxygenase pathway of AA metabolism is involved in the toxicity. Furthermore, the neurotoxic action of AA was abolished by antioxidant s 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 protectio n against AA toxicity. These results suggest that, although oxygen fre e radicals generated through lipoxygenase metabolism is responsible fo r the neurotoxicity, distinct mechanisms from those of other oxidative stress are operative in AA-induced neuronal injury.