Emerging disinfection byproducts 3-bromine carbazole induces cardiac developmental toxicity via aryl hydrocarbon receptor activation in zebrafish larvae

• Published in: Environmental pollution (1987) 2024-04, Vol.346, p.123609-123609, Article 123609
• Main Authors: Liu, Yingying, Jin, Xudong, Ye, Yanan, Xu, Zeqiong, Du, Zhongkun, Hong, Huachang, Yu, Haiying, Lin, Hongjun, Huang, Xianfeng, Sun, Hongjie
• Format: Article
• Language: English
• Subjects: 3-Bromocarbazole; abnormal development; acetylcysteine; agonists; Animals; Aryl hydrocarbon receptors; Bromine - pharmacology; cardiac output; Cardiotoxicity; Danio rerio; developmental toxicity; Disinfection; Embryo, Nonmammalian; GATA transcription factors; Heart; Larva; myocardium; pericardium; pollution; Reactive oxygen species; Receptors, Aryl Hydrocarbon - genetics; transcription (genetics); Zebrafish; Zebrafish larvae; Zebrafish Proteins - genetics
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2024.123609

3-bromine carbazole (3-BCZ) represents a group of emerging aromatic disinfection byproducts (DBP) detected in drinking water; however, limited information is available regarding its potential cardiotoxicity. To assess its impacts, zebrafish embryos were exposed to 0, 0.06, 0.14, 0.29, 0.58, 1.44 or 2.88 mg/L of 3-BCZ for 120 h post fertilization (hpf). Our results revealed that ≥1.44 mg/L 3-BCZ exposure induced a higher incidence of heart malformation and an elevated pericardial area in zebrafish larvae; it also decreased the number of cardiac muscle cells and thins the walls of the ventricle and atrium while increasing cardiac output and impeding cardiac looping. Furthermore, 3-BCZ exposure also exhibited significant effects on the transcriptional levels of genes related to both cardiac development (nkx2.5, vmhc, gata4, tbx5, tbx2b, bmp4, bmp10, and bmp2b) and cardiac function (cacna1ab, cacna1da, atp2a1l, atp1b2b, atp1a3b, and tnnc1a). Notably, N-acetyl-L-cysteine, a reactive oxygen species scavenger, may alleviate the failure of cardiac looping induced by 3-BCZ but not the associated cardiac dysfunction or malformation; conversely, the aryl hydrocarbon receptor agonist CH131229 can completely eliminate the cardiotoxicity caused by 3-BCZ. This study provides new evidence for potential risks associated with ingesting 3-BCZ as well as revealing underlying mechanisms responsible for its cardiotoxic effects on zebrafish embryos. [Display omitted] •3-BCZ exposure caused severe cardiac malformations and functional abnormalities.•3-BCZ exposure induced failure of cardiac looping.•NAC can effectively rescue 3-BCZ-induced cardiac developmental toxicity.•NAC failed to mitigate 3-BCZ-induced cardiac malformation and dysfunction.•CH223191 can effectively eliminate 3-BCZ-induced cardiotoxicity.