Assessment of the Aryl Hydrocarbon Receptor–Mediated Effects of Aromatic Sensitizers in Paper Recycling Effluent Employing Zebrafish Embryos and in Silico Docking.

Autor: Takeda, Kazuki1,2 (AUTHOR) takeda@vmas.kitasato-u.ac.jp, Sarata, Aoi1 (AUTHOR), Terasaki, Masanori3 (AUTHOR), Kubota, Akira4 (AUTHOR), Shimizu, Keita1 (AUTHOR), Kamata, Ryo1 (AUTHOR) kamata@vmas.kitasato-u.ac.jp
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Zdroj: Environmental Toxicology & Chemistry. Oct2024, Vol. 43 Issue 10, p2176-2188. 13p.
Abstrakt: Aromatic sensitizers and related substances (SRCs), which are crucial in the paper industry for facilitating color‐forming and color‐developing chemical reactions, inadvertently contaminate effluents during paper recycling. Owing to their structural resemblance to endocrine‐disrupting aromatic organic compounds, concerns have arisen about potential adverse effects on aquatic organisms. We focused on SRC effects via the aryl hydrocarbon receptor (AHR), employing molecular docking simulations and zebrafish (Danio rerio) embryo exposure assessments. Molecular docking revealed heightened binding affinities between certain SRCs in the paper recycling effluents and zebrafish Ahr2 and human AHR, which are pivotal components in the SRC toxicity mechanism. Fertilized zebrafish eggs were exposed to SRCs for up to 96 h post fertilization; among these substances, benzyl 2‐naphthyl ether (BNE) caused morphological abnormalities, such as pericardial edema and shortened body length, at relatively low concentrations (1 μM) during embryogenesis. Gene expression of cytochrome P450 1A (cyp1a) and ahr2 was also significantly increased by BNE. Co‐exposure to the AHR antagonist CH‐223191 only partially mitigated BNE's phenotypic effects, despite the effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin being relatively well restored by CH‐223191, indicating BNE's AHR‐independent toxic mechanisms. Furthermore, some SRCs, including BNE, exhibited in silico binding affinity to the estrogen receptor and upregulation of cyp19a1b gene expression. Therefore, additional insights into the toxicity of SRCs and their mechanisms are essential. The present results provide important information on SRCs and other papermaking chemicals that could help minimize the environmental impact of the paper industry. Environ Toxicol Chem 2024;43:2176–2188. © 2024 SETAC [ABSTRACT FROM AUTHOR]
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