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

Halogenated carbazoles are increasingly identified as a novel class of environmental contaminants. However, no in vivo acute toxicity information of those compounds was available. In the current 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 (2367-TCCZ), showed obvious developmental toxicity at nano-molar levels. The typical phenotypes were similar to dioxin-induced cardio-toxicity, including swollen yolk sac, pericardial sac edema, elongated and unlooped heart, and lower jaw shortening. 27-DBCZ also induced a unique pigmentation decrease during embryonic development. The CYP1A gene expression and protein staining showed both halogenated carbazoles could induce CYP1A expression at micro-molar level and primarily in the heart area, which was similar to dioxin activity. Further AhR2 gene knockdown with morpholino confirmed that the acute cardio-toxicity is AhR-dependent. In conclusion, the results of the present study demonstrate that halogenated carbazoles represent yet another class of persistent organic pollutants with dioxin-like activity in an in vivo animal model.