@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 {3512, title = {Assessment of cytotoxic and immunomodulatory properties of four antidepressants on primary cultures of abalone hemocytes (Haliotis tuberculata).}, journal = {Aquat Toxicol}, volume = {153}, year = {2014}, month = {2014 Aug}, pages = {3-11}, abstract = {

Pharmaceutical compounds like antidepressants found in surface waters raise concerns due to their potential toxicity on non-target aquatic organisms. This study aimed at investigating the in vitro cytotoxicity and immunomodulatory properties of four common antidepressants, namely Amitriptyline, Clomipramine, Citalopram and Paroxetine, on primary cultures of abalone hemocytes (Haliotis tuberculata), after 48 h-exposure. Effects on immunocompetence (phagocytosis, levels of reactive oxygen species, esterase activity and lysosomal membrane destabilization) were assessed. Results obtained by MTT assays revealed that acute toxicity is unlikely to occur in the environment since the LC50s of the four antidepressants are at the mg/L level. The different immunological endpoints displayed a biphasic response, with an increase at the lowest concentration (i.e. 1 μg/L) followed by a decrease at higher concentrations. Overall, Amitriptyline and Clomipramine, the two tricyclic antidepressants, had higher immunomodulatory capacities than the two selective serotonin reuptake inhibitors Citalopram and Paroxetine. Amitriptyline was the most potent and Citalopram the least potent drug in altering immune function in H. tuberculata.

}, keywords = {Animals, Antidepressive Agents, Cell Survival, Cells, Cultured, Enzyme Activation, Esterases, Gastropoda, Hemocytes, Immunity, Innate, Lethal Dose 50, Phagocytosis, Reactive Oxygen Species, Water Pollutants, Chemical}, issn = {1879-1514}, doi = {10.1016/j.aquatox.2013.10.020}, author = {Minguez, Laetitia and Halm-Lemeille, Marie-Pierre and Katherine Costil and Bureau, Ronan and Jean-Marc Lebel and Antoine Serpentini} } @article {3509, title = {The effect of different polychlorinated biphenyls on two aquatic models, the green alga Pseudokirchneriella subcapitata and the haemocytes from the European abalone Haliotis tuberculata.}, journal = {Chemosphere}, volume = {110}, year = {2014}, month = {2014 Sep}, pages = {120-8}, abstract = {

The present study was conducted to determine the toxicity of different polychlorinated biphenyls (PCBs) on the green algae, Pseudokirchneriella subcapitata and the haemocytes from the European abalone, Haliotis tuberculata. Using the algal growth inhibition test, the green algae median Effective Concentration (EC50) values ranged from 0.34μM for PCB28 to more than 100μM for PCBs 101 and 153. Considering the MTT viability test, the abalone EC50 values ranged from 1.67μM for PCB153 to 89μM for PCB28. Our results in contrast to previous observation in vertebrates did not show significant differences between the dioxin like- and non dioxin like-PCBs toxicities regardless of the model used. However, our results demonstrated that the toxicities of PCBs were species dependent. For example, PCB28 was the most toxic compound for P. subcapitata whereas PCBs 1, 180 and 153 were less toxic for that species. On the contrary, PCB153 was reported as the most toxic for H. tuberculata haemocytes and PCB28 the least toxic. To investigate the mode of action of these compounds, we used an in silico method. Our results suggested that PCBs have a non-specific mode of action (e.g., narcosis) on green algae, and another mode of action, probably more specific than narcosis, was reported for PCBs on the abalone haemocytes.

}, keywords = {Animals, Chlorophyta, Environmental Pollutants, Gastropoda, Hemocytes, Polychlorinated Biphenyls, Tetrachlorodibenzodioxin}, issn = {1879-1298}, doi = {10.1016/j.chemosphere.2014.02.023}, author = {Halm-Lemeille, Marie-Pierre and Abbaszadeh Fard, Elham and Latire, T and Ferard, Jean-Fran{\c c}ois and Katherine Costil and Jean-Marc Lebel and Bureau, Ronan and Antoine Serpentini} } @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} }