title: Halogenated carbazoles induce cardiotoxicity in developing zebrafish (Danio rerio) embryos.
abstract: Halogenated carbazoles are increasingly identified as a novel class of environmental contaminants. However, no in vivo acute toxicity information on those compounds was available. In the present study, an in vivo zebrafish embryonic model (Danio rerio) was used to investigate the developmental toxicity of those halogenated carbazoles. The results suggested that acute toxicity was structure-dependent. Two of the 6 tested carbazoles, 2,7-dibromocarbazole (27-DBCZ) and 2,3,6,7-tetrachlorocarbazole, showed obvious developmental toxicity at nanomolar levels. The typical phenotypes were similar to dioxin-induced cardiotoxicity, including swollen yolk sac, pericardial sac edema, elongated and unlooped heart, and lower jaw shortening. During embryonic development 27-DBCZ also induced a unique pigmentation decrease. Gene expression and protein staining of cytochrome P4501A (CYP1A) showed that both halogenated carbazoles could induce CYP1A expression at the micromolar level and primarily in the heart area, which was similar to dioxin activity. Further, aryl hydrocarbon receptor-(AhR)2 gene knockdown with morpholino confirmed that the acute cardiotoxicity is AhR-dependent. In conclusion, the results demonstrate that halogenated carbazoles represent yet another class of persistent organic pollutants with dioxin-like activity in an in vivo animal model. Environ Toxicol Chem 2016;35:2523-2529. © 2016 SETAC.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, USA. fangmingliang0711@gmail.com.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Fang
authors.affiliation: School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jiehong
authors.initials: J
authors.lastname: Guo
authors.affiliation: Cooperative Wildlife Research Laboratory and Department of Zoology, Southern Illinois University, Carbondale, Illinois, USA.
authors.forename: Da
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: An
authors.initials: A
authors.lastname: Li
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Hinton
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina, USA. dongwu2002@hotmail.com.|Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, China. dongwu2002@hotmail.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Dong
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000737:chemistry / Q000633:toxicity*; D066126:Cardiotoxicity; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000633:toxicity*; D015017:Yolk Sac / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002227:Carbazoles; D006846:Hydrocarbons, Halogenated; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins
keywords: Cytochrome P4501A; Halogenated carbazole; Toxicity; Zebrafish