PSYCHOTROPIC DELORAZEPAM INDUCES EPIGENETIC CHANGES AND RETINAL DISORDERS IN XENOPUS LAEVIS EMBRYOS

Delorazepam, a derivate 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 abuse1. Nowadays benzodiazepines are considered emerging pollutants2: conventional wastewater treatment plants indeed are unable to completely eliminate these compounds3. Consequently, they persist in the environment and bioaccumulate in non-target aquatic organisms4. The impact and consequences are still not fully clear. To collect information, we tested the effects of three increasing concentrations of delorazepam (1, 5, and 10 g/L) on Xenopus laevis embryos, a representative model of amphibians, a particularly endangered class of aquatic organisms. Results demonstrate that, besides being sedative, delorazepam is teratogenic and able to induce relevant changes in gene expression and in the oxidative state. New analysis highlighted an epigenetic effect of delorazepam, which induces an increase in methylation of the genomic DNA of the tadpoles and a differential methylation of the promotors of some early developmental genes. Parallel histological investigationhighlighted retinal disorganization, indicative of interference on the developing nervous system, and suggestive of visual defects. Results are alarming considering the growing trend of benzodiazepinesconcentrations in superficial waters5 and the fact that benzodiazepines receptors are present in all aquatic organisms.