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Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses
[Image: see text] Toxicometabolomics and biotransformation product (bioTP) elucidation were carried out in single zebrafish (ZF) embryos exposed to carbamazepine (CBZ). Exposures were conducted in 96-well plates containing six CBZ concentrations ranging from 0.5 μg/L to 50 mg/L (n = 12 embryos per d...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941598/ https://www.ncbi.nlm.nih.gov/pubmed/35166526 http://dx.doi.org/10.1021/acs.chemrestox.1c00335 |
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author | Ribbenstedt, Anton Posselt, Malte Benskin, Jonathan P. |
author_facet | Ribbenstedt, Anton Posselt, Malte Benskin, Jonathan P. |
author_sort | Ribbenstedt, Anton |
collection | PubMed |
description | [Image: see text] Toxicometabolomics and biotransformation product (bioTP) elucidation were carried out in single zebrafish (ZF) embryos exposed to carbamazepine (CBZ). Exposures were conducted in 96-well plates containing six CBZ concentrations ranging from 0.5 μg/L to 50 mg/L (n = 12 embryos per dose). In the 50 mg/L dose group, 33% of embryos developed edema during the exposure (120 hpf), while hatching was significantly delayed in three of the lower-dose groups (0.46, 3.85, and 445 μg/L) compared to the control at 48 hpf. Toxicometabolomic analysis together with random forest modeling revealed a total of 80 significantly affected metabolites (22 identified via targeted lipidomics and 58 via nontarget analysis). The wide range of doses enabled the observation of both monotonic and nonmonotonic dose responses in the metabolome, which ultimately produced a unique and comprehensive biochemical picture that aligns with existing knowledge on the mode of action of CBZ. The combination of high dose exposures and apical endpoint assessment in single embryos also enabled hypothesis generation regarding the target organ for the morphologically altering insult. In addition, two CBZ bioTPs were identified without additional exposure experiments. Overall, this work showcases the potential of toxicometabolomics and bioTP determination in single ZF embryos for rapid and comprehensive chemical hazard assessment. |
format | Online Article Text |
id | pubmed-8941598 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-89415982022-03-28 Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses Ribbenstedt, Anton Posselt, Malte Benskin, Jonathan P. Chem Res Toxicol [Image: see text] Toxicometabolomics and biotransformation product (bioTP) elucidation were carried out in single zebrafish (ZF) embryos exposed to carbamazepine (CBZ). Exposures were conducted in 96-well plates containing six CBZ concentrations ranging from 0.5 μg/L to 50 mg/L (n = 12 embryos per dose). In the 50 mg/L dose group, 33% of embryos developed edema during the exposure (120 hpf), while hatching was significantly delayed in three of the lower-dose groups (0.46, 3.85, and 445 μg/L) compared to the control at 48 hpf. Toxicometabolomic analysis together with random forest modeling revealed a total of 80 significantly affected metabolites (22 identified via targeted lipidomics and 58 via nontarget analysis). The wide range of doses enabled the observation of both monotonic and nonmonotonic dose responses in the metabolome, which ultimately produced a unique and comprehensive biochemical picture that aligns with existing knowledge on the mode of action of CBZ. The combination of high dose exposures and apical endpoint assessment in single embryos also enabled hypothesis generation regarding the target organ for the morphologically altering insult. In addition, two CBZ bioTPs were identified without additional exposure experiments. Overall, this work showcases the potential of toxicometabolomics and bioTP determination in single ZF embryos for rapid and comprehensive chemical hazard assessment. American Chemical Society 2022-02-15 2022-03-21 /pmc/articles/PMC8941598/ /pubmed/35166526 http://dx.doi.org/10.1021/acs.chemrestox.1c00335 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Ribbenstedt, Anton Posselt, Malte Benskin, Jonathan P. Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses |
title | Toxicometabolomics
and Biotransformation Product Elucidation
in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant
to Morphologically Altering Doses |
title_full | Toxicometabolomics
and Biotransformation Product Elucidation
in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant
to Morphologically Altering Doses |
title_fullStr | Toxicometabolomics
and Biotransformation Product Elucidation
in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant
to Morphologically Altering Doses |
title_full_unstemmed | Toxicometabolomics
and Biotransformation Product Elucidation
in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant
to Morphologically Altering Doses |
title_short | Toxicometabolomics
and Biotransformation Product Elucidation
in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant
to Morphologically Altering Doses |
title_sort | toxicometabolomics
and biotransformation product elucidation
in single zebrafish embryos exposed to carbamazepine from environmentally-relevant
to morphologically altering doses |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941598/ https://www.ncbi.nlm.nih.gov/pubmed/35166526 http://dx.doi.org/10.1021/acs.chemrestox.1c00335 |
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