Water contamination by delorazepam induces epigenetic defects in the embryos of the clawed frog Xenopus laevis
2023
Fogliano, Chiara | Motta, Chiara, Maria | Acloque, Hervé | Avallone, Bice | Carotenuto, Rosa | University of Naples Federico II = Università degli studi di Napoli Federico II | Génétique Animale et Biologie Intégrative (GABI) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | ANR-19-CE20-0019,PluS4PiGs,Production de véritables lignées pluripotentes porcines: une étape clé pour le phénotypage moléculaire à grande échelle des caractères agronomiques(2019)
International audience
Mostrar más [+] Menos [-]Inglés. Delorazepam, a derivative of diazepam, is a psychotropic drug belonging to the benzodiazepine class. Used as a nervous-system inhibitor, it treats anxiety, insomnia, and epilepsy, but is also associated with misuse and abuse. Nowadays benzodiazepines are considered emerging pollutants: conventional wastewater treatment plants indeed are unable to eliminate these compounds. Consequently, they persist in the environment and bioaccumulate in non-target aquatic organisms with consequences still not fully clear. To collect more information, we investigated the possible epigenetic activity of delorazepam, at three concentrations (1, 5 and 10 μg/L) using Xenopus laevis embryos as a model. Analyses demonstrated a significant increase in genomic DNA methylation and differential methylation of the promoters of some early developmental genes (otx2, sox3, sox9, pax6, rax1, foxf1, and myod1). Moreover, studies on gene expression highlighted an unbalancing in apoptosis/proliferation pathways and an aberrant expression of DNA-repair genes. Results are alarming considering the growing trend of benzodiazepine concentrations in superficial waters, especially after the peak occurred as a consequence of the pandemic COVID-19, and the fact that benzodiazepine GABA-A receptors are highly conserved and present in all aquatic organisms.
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