PBDE-47-induced oxidative stress, DNA damage and apoptosis in primary cultured rat hippocampal neurons

2,2',4,4'-Tetrabromodiphenyl ether (PBDE-47) causes developmental neurotoxicity in animal studies, but the mechanism remains poorly understood. This paper investigates the mechanism by studying the effects of oxidative stress, DNA damage, and apoptosis induced by PBDE-47 in cultured primary rat hippocampal neurons at different PBDE-47-concentrations (0, 2.06, 20.6, and 41.2 mu M). The results showed that reactive oxygen species (ROS) level, percentage of apoptosis, malondialdehyde (MDA) content, the glutathione peroxidase (GSH-Px) level and the lactic dehydrogenase (LDH) leakage rate were affected by exposure of cells to 41.2 mu M PDBE-47 (P < 0.05), but not to the lower concentrations tested (20.6 and 2.06 mu M). Reduced glutathione (GSH), superoxide dismutase (SOD), and increased DNA damage (tested by a comet assay) were affected at all concentrations tested in a dose-related manner (P < 0.05). These results suggested that PBDE-47 could induce oxidative stress, DNA damage, and apoptosis in primary rat hippocampal neurons. Whether or not this concentration response pattern indicates that ROS leads to DNA damage and/or apoptosis must be confirmed with further experiments. (c) 2007 Elsevier Inc. All rights reserved.