Danthron inhibits the neurotoxicity induced by various compounds causing oxidative damages including β-amyloid (25-35) in primary cortical cultures

Abstract

Oxidative stress caused by an elevation in reactive oxygen species (ROS) plays an important role in Alzheimer's disease and other neurodegenerative diseases. In this study, we examined the neuroprotective effect of danthron (1,8-dihydroxyanthraquinone) against neurotoxicities induced by b-amyloid (25-35), excitotoxins, apoptosis, and oxidative stress in primary cortical cultures. Danthron dose-dependently reduced neuronal injury induced by 30 μM β-amyloid (25-35). Danthron significantly inhibited oxidative injury induced by 100 μM Fe31 and decreased membrane lipid peroxidation induced by 100 μM Fe31 as measured by thiobarbituric-acid-reactive substance (TBARS). Danthron (0.5-50 μM) ameliorated the effects of buthionine sulfoximine (BSO, 1 mM), which depletes endogenous glutathione by 10-73%. Danthron also dose-dependently inhibited neuronal injury mediated by nitric oxide (NO) radicals, but failed to inhibit injury due to superoxide radicals (O2-). These results suggest danthron treatment may, in part, reduce neurotoxicity related to β-amyloid protein by both dominant inhibitory effects on membrane lipid peroxidation and glutathione deprivation. © 2004 Pharmaceutical Society of Japan.