Effect of psychiatric drugs on Daphnia magna oxylipin profiles

Neuro-active pharmaceuticals have been reported to act as endocrine disruptors enhancing reproduction in the model crustacean Daphnia manga at environmental concentrations of ng/L. Oxylipins and more specifically eicosanoids, which are lipid mediators formed from polyunsaturated fatty acids (PUFAs),...

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Veröffentlicht in:The Science of the total environment 2018-12, Vol.644, p.1101-1109
Hauptverfasser: Garreta-Lara, Elba, Checa, Antonio, Fuchs, David, Tauler, Romà, Lacorte, Silvia, Wheelock, Craig E., Barata, Carlos
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container_issue
container_start_page 1101
container_title The Science of the total environment
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creator Garreta-Lara, Elba
Checa, Antonio
Fuchs, David
Tauler, Romà
Lacorte, Silvia
Wheelock, Craig E.
Barata, Carlos
description Neuro-active pharmaceuticals have been reported to act as endocrine disruptors enhancing reproduction in the model crustacean Daphnia manga at environmental concentrations of ng/L. Oxylipins and more specifically eicosanoids, which are lipid mediators formed from polyunsaturated fatty acids (PUFAs), are known to regulate reproduction together with other physiological processes in insects. In D. magna, the biosynthesis of eicosanoids and their putative role in the regulation of reproduction has been studied using transcriptomics, genomics and exposures to cyclooxygenase inhibitors. Quantification of eicosanoids and oxylipins derived from PUFAs upon exposure to pharmaceuticals is therefore crucial for a better understanding of the mode of action of neuro-active pharmaceuticals on aquatic invertebrates. The aim of this study was to investigate shifts in the oxylipin profile in D. magna adults upon exposure to environmental concentrations of the three psychiatric drugs, fluoxetine, diazepam and carbamazepine, with known effects of enhancing offspring production. Oxylipin profiles were determined in whole organism tissues using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Up to 28 different oxylipins belonging to arachidonic (AA), linoleic acid (LA), α-linoleic acid (α-LA) and eicosapentaenoic acid (EPA) pathways were detected and quantified in D. magna adults. Exposure to the selected psychiatric drugs showed that fluoxetine enhanced the accumulation of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (12-HHTrE), whereas diazepam increased the concentration of eicosanoids belonging to the lipoxygenase (LOX) and cytochrome P450 (CYP) pathways (HETEs, EpOMEs, HODEs, HOTrEs and HEPEs) from the AA, LA, αLA and EPA pathways. Carbamazepine had little effect and only one LA-derived compound from the LOX pathway (13-HODE) increased significantly. This means that despite having different modes of action in humans, fluoxetine and diazepam up-regulated eicosanoid pathways in D. magna, closely related to known biologically active products that regulate reproduction in insects. [Display omitted] •Oxylipin profiles in D. magna adults upon exposure to low concentrations of psychiatric drugs were studied.•Up to 28 different oxylipins belonging to arachidonic, linoleic and eicosapentaenoic acid metabolic pathways were altered.•Fluoxetine increased the accumulation of the prostaglandin product 12-HHTrE.•Diazepam increased the c
doi_str_mv 10.1016/j.scitotenv.2018.06.333
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Oxylipin profiles were determined in whole organism tissues using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Up to 28 different oxylipins belonging to arachidonic (AA), linoleic acid (LA), α-linoleic acid (α-LA) and eicosapentaenoic acid (EPA) pathways were detected and quantified in D. magna adults. Exposure to the selected psychiatric drugs showed that fluoxetine enhanced the accumulation of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (12-HHTrE), whereas diazepam increased the concentration of eicosanoids belonging to the lipoxygenase (LOX) and cytochrome P450 (CYP) pathways (HETEs, EpOMEs, HODEs, HOTrEs and HEPEs) from the AA, LA, αLA and EPA pathways. Carbamazepine had little effect and only one LA-derived compound from the LOX pathway (13-HODE) increased significantly. This means that despite having different modes of action in humans, fluoxetine and diazepam up-regulated eicosanoid pathways in D. magna, closely related to known biologically active products that regulate reproduction in insects. 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Oxylipins and more specifically eicosanoids, which are lipid mediators formed from polyunsaturated fatty acids (PUFAs), are known to regulate reproduction together with other physiological processes in insects. In D. magna, the biosynthesis of eicosanoids and their putative role in the regulation of reproduction has been studied using transcriptomics, genomics and exposures to cyclooxygenase inhibitors. Quantification of eicosanoids and oxylipins derived from PUFAs upon exposure to pharmaceuticals is therefore crucial for a better understanding of the mode of action of neuro-active pharmaceuticals on aquatic invertebrates. The aim of this study was to investigate shifts in the oxylipin profile in D. magna adults upon exposure to environmental concentrations of the three psychiatric drugs, fluoxetine, diazepam and carbamazepine, with known effects of enhancing offspring production. Oxylipin profiles were determined in whole organism tissues using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Up to 28 different oxylipins belonging to arachidonic (AA), linoleic acid (LA), α-linoleic acid (α-LA) and eicosapentaenoic acid (EPA) pathways were detected and quantified in D. magna adults. Exposure to the selected psychiatric drugs showed that fluoxetine enhanced the accumulation of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (12-HHTrE), whereas diazepam increased the concentration of eicosanoids belonging to the lipoxygenase (LOX) and cytochrome P450 (CYP) pathways (HETEs, EpOMEs, HODEs, HOTrEs and HEPEs) from the AA, LA, αLA and EPA pathways. Carbamazepine had little effect and only one LA-derived compound from the LOX pathway (13-HODE) increased significantly. This means that despite having different modes of action in humans, fluoxetine and diazepam up-regulated eicosanoid pathways in D. magna, closely related to known biologically active products that regulate reproduction in insects. [Display omitted] •Oxylipin profiles in D. magna adults upon exposure to low concentrations of psychiatric drugs were studied.•Up to 28 different oxylipins belonging to arachidonic, linoleic and eicosapentaenoic acid metabolic pathways were altered.•Fluoxetine increased the accumulation of the prostaglandin product 12-HHTrE.•Diazepam increased the concentration of 12 eicosanoids and other oxylipins.•Carbamazepine had little effects only effecting one oxylipin from the linoleic acid metabolism.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30743823</pmid><doi>10.1016/j.scitotenv.2018.06.333</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3360-0729</orcidid><orcidid>https://orcid.org/0000-0002-0674-3329</orcidid><oa>free_for_read</oa></addata></record>
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subjects Animals
Daphnia - drug effects
Daphnia - physiology
Daphnia magna
Eicosanoids
Eicosapentaenoic Acid - analogs & derivatives
Fatty Acids, Unsaturated
Linoleic Acid
Medicin och hälsovetenskap
Oxylipin profiles
Oxylipins - metabolism
Psychiatric drugs
Psychotropic Drugs - toxicity
Target analysis
UPLC-MS/MS
Water Pollutants, Chemical - toxicity
title Effect of psychiatric drugs on Daphnia magna oxylipin profiles
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