DELORAZEPAM IMPAIRS THE EMBRYONIC DEVELOPMENT OF XENOPUS LAEVIS

Benzodiazepines, used for the treatment of sleep disorders, anxiety, and epilepsy, represent an important class of emerging poll-tants1. As occurs for most pharmaceutical residues, they are released into the wastewater but not degraded during sewage treatment 2therefore accumulating in effluent waters at concentrations ranging from μg/L to ng/L3. The resulting environmental concentrations may come close to human therapeutic plasmaconcentrations4. Bioaccumulation is already reported in fish 5and small crustaceans 6as significant effects on behavior, gene expression, and enzymes activity. Environmental and human health protection prompt a more accurate estimate of the impact of this drug on non-target aquatic organisms and, in particular, on early developmental stages. Therefore, in this study, we investigated the effects of the benzodiazepine Delorazepam on Xenopus laevisembryos. Environmental (1 mg/L)7and 5 and 10times higher (5 and 10 mg/L) concentrations were tested. Preliminary trials indicate that the drug reduces vitality(decreased heart rate and motility), induces marked cephalic and abdominal edema, and causes morphological alterations in the gut. At the molecular level, altered expression of developmental genes is observed together with the production of inflammatory molecules. The resulting stress condition significantly impairs embryo development and threatens their survival. Similar effects should be expected also in embryos belonging to other aquatic species though so far, they have not been considered tar-get for benzodiazepines.