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A proof of concept study demonstrating that environmental levels of carbamazepine impair early stages of chick embryonic development
Year:
2019
Source of publication :
Environment International
Authors :
Cinnamon, Yuval
;
.
Genina, Olga
;
.
Volume :
129
Co-Authors:

Kohl, A., Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Golan, N., Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Chefetz, B., Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Sela-Donenfeld, D., Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel

Facilitators :
From page:
583
To page:
594
(
Total pages:
12
)
Abstract:

Carbamazepine (CBZ)is an anticonvulsant drug used for epilepsy and other disorders. Prescription of CBZ during pregnancy increases the risk for congenital malformations. CBZ is ubiquitous in effluents and persistent during wastewater treatment. Thus, it is re-introduced into agricultural ecosystems upon irrigation with reclaimed wastewater. People consuming produce irrigated with reclaimed wastewater were found to be exposed to CBZ. However, environmental concentrations of CBZ (μg L−1)are magnitudes lower than its therapeutic levels (μg ml−1), raising the question of whether and how environmental levels of CBZ affect embryonic development. The chick embryo is a powerful and highly sensitive amniotic model system that enables to assess environmental contaminants in the living organism. Since the chick embryonic development is highly similar to mammalians, yet, it develops in an egg, toxic effects can be directly analyzed in a well-controlled system without maternal influences. This research utilized the chick embryo to test whether CBZ is embryo-toxic by using morphological, cellular, molecular and imaging strategies. Three key embryonic stages were monitored: after blastulation (st.1HH), gastrulation/neurulation (st.8HH)and organogenesis (st.15HH). Here we demonstrate that environmental relevant concentrations of CBZ impair morphogenesis in a dose- and stage- dependent manner. Effects on gastrulation, neural tube closure, differentiation and proliferation were exhibited in early stages by exposing embryos to CBZ dose as low as 0.1 μg L−1. Quantification of developmental progression revealed a significant difference in the total score obtained by CBZ-treated embryos compared to controls (up to 5-fold difference, p < 0.05). Yet, defects were unnoticed as embryos passed gastrulation/neurulation. This study provides the first evidence for teratogenic effect of environmental-relevant concentrations of CBZ in amniotic embryos that impair early but not late stages of development. These findings call for in-depth risk analysis to ensure that the environmental presence of CBZ and other drugs is not causing irreversible ecological and public-health damages. © 2019

Note:
Related Files :
Anticonvulsants
Carbamazepine
CBZ
chick embryo
congenital malformation
Environmental aspects
Epilepsy, Tonic-Clonic
Show More
Related Content
More details
DOI :
10.1016/j.envint.2019.03.064
Article number:
0
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
41406
Last updated date:
02/03/2022 17:27
Creation date:
18/06/2019 11:58
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Scientific Publication
A proof of concept study demonstrating that environmental levels of carbamazepine impair early stages of chick embryonic development
129

Kohl, A., Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Golan, N., Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Chefetz, B., Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel; Sela-Donenfeld, D., Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel

A proof of concept study demonstrating that environmental levels of carbamazepine impair early stages of chick embryonic development

Carbamazepine (CBZ)is an anticonvulsant drug used for epilepsy and other disorders. Prescription of CBZ during pregnancy increases the risk for congenital malformations. CBZ is ubiquitous in effluents and persistent during wastewater treatment. Thus, it is re-introduced into agricultural ecosystems upon irrigation with reclaimed wastewater. People consuming produce irrigated with reclaimed wastewater were found to be exposed to CBZ. However, environmental concentrations of CBZ (μg L−1)are magnitudes lower than its therapeutic levels (μg ml−1), raising the question of whether and how environmental levels of CBZ affect embryonic development. The chick embryo is a powerful and highly sensitive amniotic model system that enables to assess environmental contaminants in the living organism. Since the chick embryonic development is highly similar to mammalians, yet, it develops in an egg, toxic effects can be directly analyzed in a well-controlled system without maternal influences. This research utilized the chick embryo to test whether CBZ is embryo-toxic by using morphological, cellular, molecular and imaging strategies. Three key embryonic stages were monitored: after blastulation (st.1HH), gastrulation/neurulation (st.8HH)and organogenesis (st.15HH). Here we demonstrate that environmental relevant concentrations of CBZ impair morphogenesis in a dose- and stage- dependent manner. Effects on gastrulation, neural tube closure, differentiation and proliferation were exhibited in early stages by exposing embryos to CBZ dose as low as 0.1 μg L−1. Quantification of developmental progression revealed a significant difference in the total score obtained by CBZ-treated embryos compared to controls (up to 5-fold difference, p < 0.05). Yet, defects were unnoticed as embryos passed gastrulation/neurulation. This study provides the first evidence for teratogenic effect of environmental-relevant concentrations of CBZ in amniotic embryos that impair early but not late stages of development. These findings call for in-depth risk analysis to ensure that the environmental presence of CBZ and other drugs is not causing irreversible ecological and public-health damages. © 2019

Scientific Publication
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