Environmentally relevant uptake, elimination, and metabolic changes following early embryonic exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in zebrafish. (January 2023)

• Record Type: Journal Article
• Authors: Kossack, Michelle E.; Manz, Katherine E.; Martin, Nathan R.; Pennell, Kurt D.; Plavicki, Jessica
• Is Part Of: Chemosphere. Volume 310(2023)
• Publication Date: 2023-01
• Subjects: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin -- TCDD -- Dioxin -- Zebrafish -- High-resolution mass spectrometry -- Metabolomics -- Aryl hydrocarbon receptor -- AHR; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2022.136723
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Dioxin and dioxin-like compounds are ubiquitous environmental contaminants that induce toxicity by binding to the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. The zebrafish model has been used to define the developmental toxicity observed following exposure to exogenous AHR ligands such as the potent agonist 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD). While the model has successfully identified cellular targets of TCDD and molecular mechanisms mediating TCDD-induced phenotypes, fundamental information such as the body burden produced by standard exposure models is still unknown. We performed targeted gas chromatography (GC) high-resolution mass spectrometry (HRMS) in tandem with non-targeted liquid chromatography (LC) HRMS to quantify TCDD uptake, model the elimination dynamics of TCDD, and determine how TCDD exposure affects the zebrafish metabolome. We found that 50 ppt, 10 ppb, and 1 ppb waterborne exposures to TCDD during early embryogenesis produced environmentally relevant body burdens: 38 ± 4.34, 26.6 ± 1.2, and 8.53 ± 0.341 pg/embryo, respectively, at 24 hours post fertilization. TCDD exposure was associated with the dysregulation of metabolic pathways that are associated with the AHR signaling pathway as well as pathways shown to be affected in mammals following TCDD exposure. In addition, we discovered that TCDD exposure affected several metabolic pathways that are critical for brain development and function including glutamate metabolism, chondroitin sulfate biosynthesis, and tyrosine metabolism. Together, these data demonstrate that existing exposure methods produce environmentally relevant body burdens of TCDD in zebrafish and provide insight into the biochemical pathways impacted by toxicant-induced AHR activation. Graphical abstract: Image 1 Highlights: TCDD exposure model produces environmentally relevant body burdens in zebrafish embryos. TCDD elimination for high doses (Birnbaum, 1994; Gasaly et al., 2021) can be modeled using an exponential regression. Zebrafish exposure to TCDD alters metabolic pathways that model human exposure. Metabolomic analysis of TCDD exposed zebrafish embryos reveals new areas for neurotoxicology research.