title: Screening the oxidative potential of several mono- and di-halogenated biphenyls and biphenyl ethers in rat hepatocytes.
abstract: The present study was designed to investigate the potential of reactive oxygen species (ROS) generating and subsequent ROS-mediated lipid peroxidation (LPO) inducing effect of several mono- and di-halogenated biphenyls and biphenyl ethers in rat hepatocytes in vitro. For this aim, 4-chloro- and 4-bromo biphenyl (4-CB and 4-BB), 4-OH, 4'-BB, 4-bromo diphenylether (4-BDE), 4,4'-dichlorobiphenyl (4,4'-DCB), 4,4'-dibromobiphenyl (4,4'-DBB), and 3,4-dichlorobiphenyl (3,4-DCB) were incubated with freshly isolated rat hepatocytes. Their oxidative potential was evaluated by detecting the intracellular ROS formation by oxidant-sensing fluorescent probes (2',7'-dichlorofluorescein diacetate and C(11)-BODIPY(581/591)) using a multiplate reader and determining the levels of eight LPO products (formaldehyde, malondialdehyde, propanal, butanal, pentanal, hexanal, octanal, and nonanal) by a gas chromatography-electron capture detection. 4-BDE was found to be active both in cytoplasm and in the cell membrane in terms of inducing the formation of ROS. Another important finding was the increase in ROS-inducing potential of 4-BB when the same concentration of the hydroxylated derivative, 4-OH,4'-BB, was incubated with hepatocytes. 4-BDE was also found to be the most effective among all tested compounds in inducing LPO where 4-OH, 4'-BB was again more potent than its unmetabolized form, 4-BB. Lactate dehydrogenase leakage analyses indicated that all tested compounds are cytotoxic; 4-BDE caused the highest LDH leakage compared to other mono-halogenated biphenyls tested. Our results suggest that ROS formation by chlorinated biphenyls and mono-hydroxylated bromobiphenyls, and concomitant induction of LPO might be involved in the cytotoxic effects of these industrial pollutants. Similar effects of mono-BDE are also reported, which is a novel observation.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, Turkey. handegurer@yahoo.com
authors.forename: Hande
authors.initials: H
authors.lastname: Gurer-Orhan
authors.forename: Hilme
authors.initials: H
authors.lastname: Orhan
authors.forename: Nico P
authors.initials: NP
authors.lastname: Vermeulen
authors.forename: John H
authors.initials: JH
authors.lastname: Meerman
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004987:Ethers / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D004987:Ethers; D011075:Polybrominated Biphenyls; D017382:Reactive Oxygen Species; D011078:Polychlorinated Biphenyls; D007770:L-Lactate Dehydrogenase