Metabolomics to study the sublethal effects of diazepam and irbesartan on glass eels (Anguilla anguilla)

• Published in: Aquatic Toxicology
• Main Authors: Alvarez-Mora, Iker, Bolliet, Valérie, Lopez-Herguedas, Naroa, Olivares, Maitane, Monperrus, Mathilde, Etxebarria, Nestor
• Other Authors: University of the Basque Country = Euskal Herriko Unibertsitatea (UPV / EHU), Aquapôle, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecologie Comportementale et Biologie des Populations de Poissons (ECOBIOP), Université de Pau et des Pays de l'Adour (UPPA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Pau et des Pays de l'Adour (UPPA)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2023
• Subjects: Glass eels; Metabolomics; Mass spectrometry; Non -target analysis; Exposomics; Lipidomics; [SDV.TOX]Life Sciences [q-bio]/Toxicology; Anguilla anguilla
• Online Access: https://hal.inrae.fr/hal-04525967; https://doi.org/10.1016/j.aquatox.2023.106547

International audience Since glass eels are continuously exposed to contamination throughout their migratory journey in estuaries, to a certain extent the fall in the population of this endangered species might be attributed to this exposure, which is especially acute in estuaries under high urban pressure. In this work, metabolomics was used to address the main objective of this study, to evaluate the effects of two pharmaceuticals previously identified as potential con-cerning chemicals for fish (diazepam and irbesartan) on glass eels. An exposure experiment to diazepam, irbe-sartan and their mixture was carried out over 7 days followed by 7 days of depuration phase. After exposure, glass eels were individually sacrificed using a lethal bath of anesthesia, and then an unbiased sample extraction method was used to extract separately the polar metabolome and the lipidome. The polar metabolome was submitted to targeted and non-targeted analysis, whereas for the lipidome only the non-targeted analysis was carried out. A combined strategy using partial least squares discriminant analysis and univariate and multivariate statistical analysis (ANOVA, ASCA, t-test, and fold-change analysis) was used to identify the metabolites altered in the exposed groups with respect to the control group. The results of the polar metabolome analysis revealed that glass eels exposed to the diazepam-irbesartan mixture were the most impacted ones, with altered levels for 11 metabolites, some of them belonging to the energetic metabolism, which was confirmed to be sensitive to these contaminants. Additionally, the dysregulation of the levels of twelve lipids, most of them with energetic and structural functions, was also found after exposure to the mixture, which might be related to oxidative stress, inflammation, or alteration of the energetic metabolism.