Assessment of the neurotoxic mechanisms of decabrominated diphenyl ether (PBDE-209) in primary cultured neonatal rat hippocampal neurons includes alterations in second messenger signaling and oxidative stress.
2',2',3',3',4',4',5',5',6',6',-decabrominated diphenyl ether (PBDE-209) is the most widely used polybrominated diphenyl ethers (PBDEs) globally. Some animal experiments have found that PBDE-209 caused developmental neurotoxicity. But detailed mechanisms are less well understood. Our experiments were conducted to research the potential neurotoxic mechanisms of PBDE-209 in primary cultured neonatal rat hippocampal neurons by measuring cell viability, apoptotic rate, expression of P38 mitogen-activated protein kinases (MAPKs), calcium ion concentration, oxidative stress, nitrous oxide (NO) content, and global gene DNA methylation levels. The neurons were exposed to different PBDE-209 concentrations (0, 10, 30 and 50 microg/ml). The difference between the experimental groups and control groups was significant (P<0.05). PBDE-209 increased the rate of apoptosis, expression of P38 MAPK, calcium ion concentration, reactive oxygen species (ROS) level, malondialdehyde (MDA) content and NO content (P<0.05). In addition, PBDE-209 deceased cell viability, activity of superoxide dismutase (SOD) and the levels of global gene DNA methylation (P<0.05). The results suggested that PBDE-209 could affect secondary messengers, cause oxidative stress and decrease global gene DNA methylation levels. These actions may contribute to the mechanism of PBDE-209 neurotoxicity.
Chen
Jingsi
J
The Third Affiliated Hospital of Guangzhou Medical College, Institute of Gynecology and Obstetrics, Guangzhou, China.
Liufu
Chun
C
Sun
Weiwen
W
Sun
Xiaofang
X
Chen
Dunjin
D
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009609:Nitrous Oxide / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D015290:Second Messenger Systems / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000187:drug effects
D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; D009609:Nitrous Oxide; C010902:decabromobiphenyl ether; D002118:Calcium