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Acute toxicity of 8 antidepressants: what are their modes of action?

TitreAcute toxicity of 8 antidepressants: what are their modes of action?
Type de publicationJournal Article
Year of Publication2014
AuteursMinguez, L, Farcy, E, Ballandonne, C, Lepailleur, A, Serpentini, A, Lebel, J-M, Bureau, R, Halm-Lemeille, M-P
JournalChemosphere
Volume108
Pagination314-9
Date Published2014 Aug
ISSN1879-1298
Mots-clésAnimals, Antidepressive Agents, Cell Survival, Cells, Cultured, Daphnia, Environmental Pollutants, Gastropoda, Hemocytes, Lysosomes, Models, Molecular, Phosphatidylcholines, Serotonin Uptake Inhibitors
Résumé

Currently, the hazard posed by pharmaceutical residues is a major concern of ecotoxicology. Most of the antidepressants belong to a family named the Cationic Amphipathic Drugs known to have specific interactions with cell membranes. The present study assessed the impact of eight antidepressants belonging to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors by the combination of multi-approaches (in vivo, in vitro, in silico) and gives some insights on the mode of action for these molecules. Antidepressants were from the most to the least toxic compound for Daphnia magna: Sertraline (EC50=1.15 mg L(-1))>Clomipramine (2.74 mg L(-1))>Amitriptyline (4.82 mg L(-1))>Fluoxetine (5.91 mg L(-1))>Paroxetine (6.24 mg L(-1))>Mianserine (7.81 mg L(-1))>Citalopram (30.14 mg L(-1)) and Venlafaxine (141.28 mg L(-1)). These acute toxicities were found correlated to Log Kow coefficients (R=0.93, p<0.001) and to cytotoxicity assessed on abalone hemocytes through the neutral red uptake assay (R=0.96, p<0.001). If narcosis as mode of action is typically expected during acute ecotoxicity bioassays, we showed by molecular modeling that particular interactions can exist between antidepressants and phosphatidylcholine, a major component of cell membranes, leading to a more specific mode of action corresponding to a potential acidic hydrolysis of ester functions.

DOI10.1016/j.chemosphere.2014.01.057
Alternate JournalChemosphere
Identifiant (ID) PubMed24534154