@article {3510, title = {Acute toxicity of 8 antidepressants: what are their modes of action?}, journal = {Chemosphere}, volume = {108}, year = {2014}, month = {2014 Aug}, pages = {314-9}, abstract = {

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.

}, keywords = {Animals, Antidepressive Agents, Cell Survival, Cells, Cultured, Daphnia, Environmental Pollutants, Gastropoda, Hemocytes, Lysosomes, Models, Molecular, Phosphatidylcholines, Serotonin Uptake Inhibitors}, issn = {1879-1298}, doi = {10.1016/j.chemosphere.2014.01.057}, author = {Minguez, Laetitia and Farcy, E and Ballandonne, C{\'e}line and Lepailleur, Alban and Antoine Serpentini and Jean-Marc Lebel and Bureau, Ronan and Halm-Lemeille, Marie-Pierre} } @article {3428, title = {Comparison of the sensitivity of seven marine and freshwater bioassays as regards antidepressant toxicity assessment.}, journal = {Ecotoxicology}, volume = {23}, year = {2014}, month = {2014 Nov}, pages = {1744-54}, abstract = {

The hazards linked to pharmaceutical residues like antidepressants are currently a major concern of ecotoxicology because they may have adverse effects on non-target aquatic organisms. Our study assesses the ecotoxicity of three antidepressants (fluoxetine, sertraline and clomipramine) using a battery of marine and freshwater species representing different trophic levels, and compares the bioassay sensitivity levels. We selected the following bioassays: the algal growth inhibition test (Skeletonema marinoi and Pseudokirchneriella subcapitata), the microcrustacean immobilization test (Artemia salina and Daphnia magna), development and adult survival tests on Hydra attenuata, embryotoxicity and metamorphosis tests on Crassostrea gigas, and in vitro assays on primary cultures of Haliotis tuberculata hemocytes. The results showed high inter-species variability in EC50-values ranging from 43 to 15,600\ {\textmu}g/L for fluoxetine, from 67 to 4,400\ {\textmu}g/L for sertraline, and from 4.70\ {\textmu}g/L to more than 100,000\ {\textmu}g/L for clomipramine. Algae (S. marinoi and P. subcapitata) and the embryo-larval stages of the oyster C. gigas were the most sensitive taxa. This raises an issue due to their ecological and/or economic importance. The marine crustacean A. salina was the least sensitive species. This difference in sensitivity between bioassays highlights the importance of using a test battery.

}, issn = {1573-3017}, doi = {10.1007/s10646-014-1339-y}, author = {Minguez, Laetitia and Di Poi, C and Farcy, E and Ballandonne, C{\'e}line and Benchouala, Amira and Bojic, Cl{\'e}ment and Cossu-Leguille, Carole and Katherine Costil and Antoine Serpentini and Jean-Marc Lebel and Halm-Lemeille, Marie-Pierre} } @article {3370, title = {Protecting honey bees: identification of a new varroacide by in silico, in vitro, and in vivo studies.}, journal = {Parasitol Res}, volume = {113}, year = {2014}, month = {2014 Dec}, pages = {4601-10}, abstract = {

Varroa destructor is the main concern related to the gradual decline of honeybees. Nowadays, among the various acaricides used in the control of V. destructor, most presents increasing resistance. An interesting alternative could be the identification of existent molecules as new acaricides with no effect on honeybee health. We have previously constructed the first 3D model of AChE for honeybee. By analyzing data concerning amino acid mutations implicated in the resistance associated to pesticides, it appears that pirimicarb should be a good candidate for varroacide. To check this hypothesis, we characterized the AChE gene of V. destructor. In the same way, we proposed a 3D model for the AChE of V. destructor. Starting from the definition of these two 3D models of AChE in honeybee and varroa, a comparison between the gorges of the active site highlighted some major differences and particularly different shapes. Following this result, docking studies have shown that pirimicarb adopts two distinct positions with the strongest intermolecular interactions with VdAChE. This result was confirmed with in vitro and in vivo data for which a clear inhibition of VdAChE by pirimicarb at 10 μM (contrary to HbAChE) and a 100\% mortality of varroa (dose corresponding to the LD50 (contact) for honeybee divided by a factor 100) were observed. These results demonstrate that primicarb could be a new varroacide candidate and reinforce the high relationships between in silico, in vitro, and in vivo data for the design of new selective pesticides.

}, issn = {1432-1955}, doi = {10.1007/s00436-014-4150-z}, author = {Dulin, Fabienne and C{\'e}line Zatylny-Gaudin and Ballandonne, C{\'e}line and Guillet, Bertrand and Bonafos, Romain and Bureau, Ronan and Halm, Marie Pierre} }