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In Vitro Antioxidant Neuroprotective Activity of BN 80933, a Dual Inhibitor of Neuronal Nitric Oxide Synthase and Lipid Peroxidation
Author(s) -
DemerléPallardy Caroline,
GillardRoubert Véronique,
Marin JeanGrégoire,
Auguet Michel,
Chabrier PierreEtienne
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742079.x
Subject(s) - trolox , lipid peroxidation , glutathione , neuroprotection , nitric oxide synthase , chemistry , pharmacology , buthionine sulfoximine , antioxidant , nitric oxide , biochemistry , oxidative stress , biology , enzyme , organic chemistry , dpph
BN 80933, a dual inhibitor of neuronal nitric oxide synthase and lipid peroxidation, prevents in vivo brain ischemic/reperfusion injury. In the present study, BN 80933 was shown to protect neurons from hypoxia‐induced cell death in primary cultures of cortical neurons. BN 80933 prevented lactate dehydrogenase activity elevation induced by hypoxia, displaying an IC 50 value of 0.15 ± 0.05 μ M . This effect was likely due to the antioxidant properties of BN 80933 because Trolox, but not N G ‐nitro‐L‐arginine, also elicited protection. The antioxidant property of BN 80933 was then further investigated on HT‐22 cells subjected to buthionine sulfoximine‐ or glutamate‐induced glutathione depletion. The relative order of potency of the various compounds to inhibit oxidative stress‐induced neuronal death (BN 80933 > U104067 > butylated hydroxytoluene > 17β‐estradiol > Trolox > vitamin E) correlated with their ability to inhibit brain membrane lipid peroxidation (correlation coefficient = 0.939). BN 80933 afforded protection even when added 6 h after glutamate exposure. BN 80933 did not reverse intracellular glutathione depletion but prevented elevation of the level of 8‐epiprostaglandin F 2α (8‐isoprostane), which appeared to be a delayed phenomenon. In conclusion, BN 80933 induces a potent cytoprotection that may be mediated by inhibition of delayed lipid peroxidation.