linoleic-acid and 12-hydroxy-5-8-10-heptadecatrienoic-acid

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.

Topics: Animals; Daphnia; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Linoleic Acid; Oxylipins; Psychotropic Drugs; Water Pollutants, Chemical

The effects of fatty acyl coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl--CoA) on the activities of lipoxygenase and cyclooxygenase in rabbit platelets were examined. Palmitoyl-, stearoyl-, oleoyl- and linoleoyl- CoA were potent inhibitors of platelet lipoxygenase activity. In addition to the lipoxygenase, the four fatty acyl-CoA esters elicited inhibitory activity on platelet cyclooxygenase, although the inhibition was a little weaker. The CoA derivative of the icosanoid precursor arachidonic acid (AA) showed little inhibition on lipoxygenase and cyclooxygenase. Palmitic, stearic and oleic acids had little or no effect on lipoxygenase and cyclooxygenase, in contrast with their CoA derivatives. Linoleic acid was more potent than linoleoyl-CoA as an inhibitor of the cyclooxygenase, but it was a weak inhibitor of the lipoxygenase. These results suggest that the CoA derivatives of palmitic, stearic, oleic and linoleic acids have the potential to modulate both platelet lipoxygenase and cyclooxygenase activities and may have functional effects within platelets.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acyl Coenzyme A; Animals; Arachidonic Acid; Blood Platelets; Cyclooxygenase Inhibitors; Esters; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Linoleic Acid; Linoleic Acids; Lipoxygenase; Lipoxygenase Inhibitors; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Prostaglandin-Endoperoxide Synthases; Rabbits; Stearic Acids; Thromboxane B2

We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Blood Platelets; Chromatography, High Pressure Liquid; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Indomethacin; Linoleic Acid; Linoleic Acids; Linoleic Acids, Conjugated; Platelet Activation; Stereoisomerism; Toxoplasma