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Environ Toxicol Chem. 2016 Oct;35(10):2523-2529. doi: 10.1002/etc.3416. Epub 2016 Jun 21.

Halogenated carbazoles induce cardiotoxicity in developing zebrafish (Danio rerio) embryos.

Author information

1
Nicholas School of the Environment, Duke University, Durham, North Carolina, USA. fangmingliang0711@gmail.com.
2
School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.
3
Cooperative Wildlife Research Laboratory and Department of Zoology, Southern Illinois University, Carbondale, Illinois, USA.
4
Nicholas School of the Environment, Duke University, Durham, North Carolina, USA.
5
Nicholas School of the Environment, Duke University, Durham, North Carolina, USA. dongwu2002@hotmail.com.
6
Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia, China. dongwu2002@hotmail.com.

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.

KEYWORDS:

Cytochrome P4501A; Halogenated carbazole; Toxicity; Zebrafish

PMID:
26932193
DOI:
10.1002/etc.3416
[Indexed for MEDLINE]

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