Halogenated carbazoles induce cardiotoxicity in developing zebrafish (<i>Danio rerio</i>) embryos

Fang, Mingliang; Guo, Junmeng; Chen, Da; Liu, An; Hinton, David E.; Dong, Wei

doi:10.1002/etc.3416

Cited by 61 publications

(32 citation statements)

References 19 publications

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“…In particular, the zebrafish has a high cost-effect benefit and has become an important tool to evaluate Geno-cardiotoxicity, to study embryo development and general toxicity . For instance, several compound screens, including some evaluating drug-induced cardiotoxicity and others already in preclinical trials, have successfully tested drug effects in zebrafish [27][28][29] .…”

Section: Zebrafish As Cardiotoxicological Toolmentioning

confidence: 99%

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

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Embryonic and larval Danio rerio (zebrafish) is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features high genetic homology to mammals, robust, phenotypes, highthroughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN and TALEN make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies employing zebrafish as experimental model, comparing it with other in vivo and in vitro models, presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity and efficacy in order to facilitate more extensive, easy and comprehensive knowledge of new generation drugs.

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Section: Zebrafish As Cardiotoxicological Toolmentioning

confidence: 99%

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

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“…Dong and his group [6] tested cardiotoxicity of six carbazole compounds and found that out of the six carbazoles, two, namely 2,7-dibromocarbazole and 2,3,6,7-tetrachlorocarbazole, were more toxic than the rest. These two carbazoles produced phenotypes similar to dioxin-induced phenotypes, including pericardial edema and straight elongated hearts in zebrafish embryos at nanomolar concentrations.…”

Section: Toxic Substances Causing Heart Defects In Zebrafishmentioning

confidence: 99%

“…These two carbazoles produced phenotypes similar to dioxin-induced phenotypes, including pericardial edema and straight elongated hearts in zebrafish embryos at nanomolar concentrations. Morpholino knockdown of the aryl hydrocarbon receptor 2 (AhR-2) gene rescued carbazole-induced defects, which indicates that the acute cardiotoxicity was AhR dependent [6]. …”

Section: Toxic Substances Causing Heart Defects In Zebrafishmentioning

confidence: 99%

“…Because of their chemical stability, dioxins accumulate in the environment, enter the food chain, and concentrate in fat tissue. Likewise, halogenated carbazole derivatives, a class of compounds containing tricyclic aromatic heterocycles, are reportedly increasing in the environment, specifically in rivers, lake sediments and soils [6,7,8,9]. Polycyclic aromatic hydrocarbons like benzopyrene (a compound generated from incomplete combustion of carbon) and phenanthrene (the most abundant component of coal tar) are ubiquitous contaminants.…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

Sarmah

2016

IJMS

126

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Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed.

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“…These nitrogen containing heterocyclic compounds such as the mono-and polyhalogenated carbazoles (PHCZs) which are commonly known as nitrogenated dioxins are suggested to originate from either anthropogenic or natural sources and have been reported to possess toxicities comparable to those of dioxin and furan compounds basically because of their structural similarities [92]. From a chemical standpoint, the toxicity of polyhalogenated carbazoles (PHCZs) has been attributed to their resemblance with polychlorinated dibenzo-p-dioxin and dibenzofuran, with very close correlation between their planar molecular conformation and dioxin-like toxicological characteristics [23]. Carbazole in particular has been reported in literature to be both carcinogenic and mutagenic [45].…”

Section: Nitrogenated Analogues Of Dioxins Dibenzofurans and Their Cmentioning

confidence: 99%

A review of persistent organic pollutants: dioxins, furans, and their associated nitrogenated analogues

et al. 2020

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Dioxins and furans are no doubt the most notorious class of organochlorine toxicants in the environmental system whose adverse effects are detrimental to public health with extreme negative economic impacts. Polychlorinated dibenzop-dioxin and dibenzofurans and dioxin-like compounds such as the polychlorinated biphenyls, carbazoles are in the class of persistent organic pollutants-prioritized under the Stockholm convention as the "dirty dozens", besides being listed as group 1 human carcinogens by the International Agency for Research on Cancer. Because of their recalcitrant nature in the environment, bioaccumulation in lipids of cells of animals and their general toxicities, this family of compounds has received increased scientific interest in pollution and toxicology research. Accumulation of these toxicants in lipids of animals, and human exposure has been traced to animal products such as meat, eggs, milk and fish. Combustion events, industrial and municipal waste incineration practices, open fires and some industrial activities especially those dealing with metallurgy are well-established sources of these environmental contaminants. The critical aspects of dioxins, furans and their analogues; notably their sources their mechanistic formation by precursor initiation, de novo pathways, how they manifest their toxicity by activation of aryl hydrocarbon receptor, detoxification of these chemicals from the environment and the analytical methods used to quantify and detect from environmental sample matrices has been explored in this work. This review also provides an in-depth examination of the toxic characteristic behaviour of dioxins and furans, polycyclic aromatic hydrocarbons as well as the emerging nitrogenated analogues of dioxins such as polychlorinated carbazole, and carbazole itself.

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

Cited by 61 publications

References 19 publications

Zebrafish as Toxicological model for screening and recapitulate human diseases

Zebrafish as Toxicological model for screening and recapitulate human diseases

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

A review of persistent organic pollutants: dioxins, furans, and their associated nitrogenated analogues

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