Fogliano, Chiara (2023) Benzodiazepine effects on non-target organisms. [Tesi di dottorato]

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Abstract

Benzodiazepines, psychotropic drugs for the treatment of insomnia and anxiety, are among the most prescribed remedies worldwide. The massive use and abuse results in the release of active principles and metabolites in the wastewater, where they persist since not eliminated by sewage treatments. They are therefore considered emerging contaminants of great environmental hazard, even at low concentrations, also considering that receptors for benzodiazepines are found in all animals and plants. The fate and consequences of benzodiazepine exposure in aquatic organisms are not fully clear: a large variety of these drugs is available on the market, and a plethora of direct and indirect effects could be exerted on different, accidentally exposed non-target species. This Ph.D. project represents the first comparative and multidisciplinary study carried out in parallel on six models, five animals and one plant, with the aim of understanding the extent of the effects of delorazepam, a common-used long-life, and high-potency benzodiazepine. Three concentrations were tested: 1 µg/L, considered environmentally realistic, and 5 and 10 µg/L, considered near-future concentrations based on growing consumption trends worldwide. Behavioural, developmental, and cyto-toxicological effects were considered; standard locomotory and phototactic tests were conducted to determine the effects of delorazepam on nervous and sensory activity. Conventional toxicity tests were performed to clarify the impact on early development and embryo growth, while cytological approaches, by light and electron microscopy, were employed to highlight effects on cell organization and functionality. Finally, molecular and biochemical investigations were carried out to deepen the possible interference with gene expression and protein patterns.

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