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

作者: Ayelet Kohl , Naama Golan , Yuval Cinnamon , Olga Genin , Benny Chefetz

DOI: 10.1016/J.ENVINT.2019.03.064

关键词: EmbryogenesisMorphogenesisEmbryoAndrologyNeurulationNeural tubeCarbamazepineBiologyBlastulaTeratology

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

参考文章(117)
Raman Sankar, Jason T. Lerner, Teratogenicity of antiepileptic drugs: role of pharmacogenomics. International Review of Neurobiology. ,vol. 83, pp. 215- 225 ,(2008) , 10.1016/S0074-7742(08)00012-3
Anticonvulsant drugs in bipolar disorder. Dialogues in clinical neuroscience. ,vol. 1, pp. 24- 40 ,(1999) , 10.31887/DCNS.1999.1.1/HGRUNZE
Masanori Uchikawa, Megumi Yoshida, Makiko Iwafuchi-Doi, Kazunari Matsuda, Yoshiko Ishida, Tatsuya Takemoto, Hisato Kondoh, B1 and B2 Sox gene expression during neural plate development in chicken and mouse embryos: universal versus species-dependent features. Development Growth & Differentiation. ,vol. 53, pp. 761- 771 ,(2011) , 10.1111/J.1440-169X.2011.01286.X
Kristin H. Kain, James W.I. Miller, Celestial R. Jones-Paris, Rebecca T. Thomason, John D. Lewis, David M. Bader, Joey V. Barnett, Andries Zijlstra, The chick embryo as an expanding experimental model for cancer and cardiovascular research. Developmental Dynamics. ,vol. 243, pp. 216- 228 ,(2014) , 10.1002/DVDY.24093
António F Ambrósio, Patrício Soares-da-Silva, Caetana M Carvalho, Arsélio P Carvalho, None, Mechanisms of Action of Carbamazepine and Its Derivatives, Oxcarbazepine, BIA 2-093, and BIA 2-024* Neurochemical Research. ,vol. 27, pp. 121- 130 ,(2002) , 10.1023/A:1014814924965
Nicole Le Douarin, Chaya Kalcheim, The neural crest Cambridge University Press. ,(1999) , 10.1017/CBO9780511897948
RO Hynes, R Patel, RH Miller, Migration of neuroblasts along preexisting axonal tracts during prenatal cerebellar development The Journal of Neuroscience. ,vol. 6, pp. 867- 876 ,(1986) , 10.1523/JNEUROSCI.06-03-00867.1986
Elizabeth N. Schock, Ching-Fang Chang, Ingrid A. Youngworth, Megan G. Davey, Mary E. Delany, Samantha A. Brugmann, Utilizing the chicken as an animal model for human craniofacial ciliopathies Developmental Biology. ,vol. 415, pp. 326- 337 ,(2016) , 10.1016/J.YDBIO.2015.10.024
Lauren A. Kristofco, Luis Colon Cruz, Samuel P. Haddad, Martine L. Behra, C. Kevin Chambliss, Bryan W. Brooks, Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine Aquatic Toxicology. ,vol. 170, pp. 344- 354 ,(2016) , 10.1016/J.AQUATOX.2015.09.011