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

Mingliang Fang, Jiehong Guo, Da Chen, An Li, David E. Hinton, Wu Dong

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44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2523-2529
Number of pages7
JournalEnvironmental Toxicology and Chemistry
Volume35
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
The present study was supported by the National Natural Science Foundation of China (21267015, 81360508, and 21567019), the Natural Science Foundation of Inner Mongolia Autonomous Region of China (2015MS0804), Prairie Excellence Specialist (2013), a project of scientific and technical innovation of the Inner Mongolia Autonomous Region (2015-2016), the US Environmental Protection Agency under National Science Foundation Cooperative Agreement EF-0830093, and the Center for the Environmental Implications of NanoTechnology. We appreciate the donation of CYP1A antibody by J. Stegeman from the Woods Hole Oceanographic Institution. We also thank R. Di Giulio from the Nicholas School of the Environment, Duke University, for the use of the microinjection equipment.

Publisher Copyright:
© 2016 SETAC

Keywords

  • Cytochrome P4501A
  • Halogenated carbazole
  • Toxicity
  • Zebrafish

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