title: Cytotoxic effects and oxidative stress response of six PBDE metabolites on human L02 cells.
abstract: In the present study, the cytotoxic effects and toxicological mechanism of six polybrominated diphenyl ethers (PBDEs) metabolites (3-OH-BDE47, 3-MeO-BDE47, 5-OH-BDE47, 5-MeO-BDE47, 6-OH-BDE85 and 6-MeO-BDE85) on L02 cells were explored by investigating the cell viability, apoptosis, lactic dehydrogenase (LDH) leakage, and oxidative stress response. The results showed that these metabolites could inhibit cell proliferation and induce apoptosis, among which 6-OH-BDE85 had the highest efficiency. LDH leakage test also showed that 6-OH-BDE85 had the strongest ability to cause LDH release. The reactive oxygen species (ROS) levels in 6-OH-BDE85- and 3-OH-BDE47-treated groups were significantly elevated in a dose-dependent manner. After treatment for 24 h, four BDE47 metabolites (3-OH-BDE47, 3-MeO-BDE47, 5-OH-BDE47, and 5-MeO-BDE47) induced an increase in superoxide dismutase (SOD) activity and decrease in glutathione (GSH) level, whereas 6-OH-BDE85 led to a decrease in both SOD activity and GSH level. These effects disappeared after continued culturing for another 24 h. In conclusion, these PBDE metabolites, especially 6-OH-BDE85, showed cytotoxicity on L02 cells, which was at least partially related to the oxidative stress level.
authors.affiliation: Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University, Shanghai, PR China.
authors.forename: Yu F
authors.initials: YF
authors.lastname: Zhong
authors.forename: Liu L
authors.initials: LL
authors.lastname: Wang
authors.forename: Ling L
authors.initials: LL
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: Mei L
authors.initials: ML
authors.lastname: Hou
authors.forename: Ke W
authors.initials: KW
authors.lastname: Zheng
authors.forename: Xin Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: Ming H
authors.initials: MH
authors.lastname: Wu
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Yu
authors.forename: Guo Y
authors.initials: GY
authors.lastname: Sheng
authors.forename: Jia M
authors.initials: JM
authors.lastname: Fu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; D017382:Reactive Oxygen Species; C511295:2,2',4,4'-tetrabromodiphenyl ether; D013482:Superoxide Dismutase; D005978:Glutathione