Danthron inhibits the neurotoxicity induced by various compounds causing oxidative damages including beta-amyloid (25-35) in primary cortical cultures.
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 beta-amyloid (25-35), excitotoxins, apoptosis, and oxidative stress in primary cortical cultures. Danthron dose-dependently reduced neuronal injury induced by 30 microM beta-amyloid (25-35). Danthron significantly inhibited oxidative injury induced by 100 microM Fe(3+) and decreased membrane lipid peroxidation induced by 100 microM Fe(3+) as measured by thiobarbituric-acid-reactive substance (TBARS). Danthron (0.5-50 microM) 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 (O(2-)). These results suggest danthron treatment may, in part, reduce neurotoxicity related to beta-amyloid protein by both dominant inhibitory effects on membrane lipid peroxidation and glutathione deprivation.
Kwon
Yong-Soo
YS
Neurotoxicology Program, Department of Pharmacy, College of Pharmacy, Kangwon National University, Korea.
Koh
Jae-Young
JY
Song
Dong-Keun
DK
Kim
Hyoung-Chun
HC
Kwon
Myung-Sang
MS
Choi
Yeon-Sik
YS
Wie
Myung-Bok
MB
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D000880:Anthraquinones; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C004315:danthron