title: BDE-99 congener induces cell death by apoptosis of human hepatoblastoma cell line - HepG2.
abstract: Polybrominated Diphenyl Ethers (PBDEs) are an important class of flame retardants with a wide range of toxic effects on biotic and abiotic systems. The toxic mechanisms of PBDEs are still not completely understood because there are several different congeners with different chemical and biological characteristics. BDE-99 is one of these, widely found in the environment and biological samples, showing evidence of neurotoxic and endocrine disruption activities, but with little information about its action mechanism described in the current literature. This work investigated the effects of BDE-99 on the HepG2 cell line in order to clarify its toxic mechanism, using concentrations of 0.5-25 μM (24 and 48 h). Our results showed that BDE-99 could cause cell death in the higher concentrations, its activity being related to a decrease in mitochondrial membrane potential and an accumulation of ROS. It was also shown that BDE-99 induced the exposure of phosphatidylserine, caspases 3 and 9 activation and DNA fragmentation in HepG2 cells, without causing the release of LDH. Thus it was shown that BDE-99 could cause HepG2 cell death by apoptosis, suggesting its toxicity to the human liver.
authors.affiliation: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Departamento de Química, Universidade de São Paulo, Av. Bandeirantes, 3900, CEP:14040-901, Bairro Monte Alegre, Ribeirão Preto, São Paulo, Brazil. lekasouza@gmail.com.
authors.forename: A O
authors.initials: AO
authors.lastname: Souza
authors.forename: L C
authors.initials: LC
authors.lastname: Pereira
authors.forename: D P
authors.initials: DP
authors.lastname: Oliveira
authors.forename: D J
authors.initials: DJ
authors.lastname: Dorta
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C477694:2,2',4,4',5-brominated diphenyl ether; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053453:Caspase 9