Screening the oxidative potential of several mono- and di-halogenated biphenyls and biphenyl ethers in rat hepatocytes

Comb Chem High Throughput Screen. 2006 Jul;9(6):449-54. doi: 10.2174/138620706777698517.


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.

MeSH terms

  • Animals
  • Drug Evaluation, Preclinical
  • Ethers / chemistry
  • Ethers / pharmacology*
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism*
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Polybrominated Biphenyls / chemistry
  • Polybrominated Biphenyls / pharmacology*
  • Polychlorinated Biphenyls / chemistry
  • Polychlorinated Biphenyls / pharmacology*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*


  • Ethers
  • Polybrominated Biphenyls
  • Reactive Oxygen Species
  • Polychlorinated Biphenyls
  • L-Lactate Dehydrogenase