15-hydroxy-5-8-11-13-eicosatetraenoic-acid and linoleylanilide

N-phenyllinoleamide (NPLA) has been detected as extraneous compound in adulterated cooking oils associated with a unique epidemic disease known as the Toxic Oil Syndrome (TOS). In this communication we report on the action of NPLA on the endogenous cyclooxygenase and lipoxygenase arachidonate metabolism. Results show that mouse peritoneal macrophages (MPM) exposed to 1 mM NPLA for 2 h undergo significant increases of 6-keto prostaglandin F1a, prostaglandin E2, leukotriene B4, 12- and 15-hydroxyeicosatetraenoic acids. MPM prelabelled with 3H-AA showed an enhanced release when exposed to NPLA. Thus, it is concluded that NPLA potentiates AA release from cell membrane phospholipids and the subsequent cyclooxygenase and lipoxygenase oxidative metabolism of this precursor to various eicosanoids. This is in agreement with the implication of peroxidative process mediated by fatty acids anilides in TOS.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Analysis of Variance; Anilides; Animals; Arachidonic Acid; Brassica; Cells, Cultured; Fatty Acids, Monounsaturated; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Linoleic Acids; Lipoxygenase; Macrophages; Male; Mice; Peritoneal Cavity; Plant Oils; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Radioimmunoassay; Rapeseed Oil; Thromboxanes

N-phenyllinoleamide (NPLA) is a useful marker for adulterated oil samples associated with cases of toxic oil syndrome (TOS). To date, NPLA has not reproduced the human poisoning episode in experimental animal models and, thus, its pathological role in the syndrome remains controversial. The present report describes the effect of NPLA on the lipoxygenase metabolism of exogenous arachidonic acid (AA) in mouse peritoneal macrophages (MPM). Results show that MPM cells exposed to 1mM NPLA for 2 h, when subsequently incubated with exogenous 3H-AA, undergo a significant increase in the biosynthesis of 3H-12-hydroxyeicosatetraenoic acid (3H-12-HETE) whereas levels of 3H-15-HETE are relatively stable. These data indicate that NPLA selectively potentiates the lipoxygenase metabolism of exogenous AA, supporting the possible implication of lipid peroxidative processes in the ethiopathology of TOS, although the relatively high NPLA concentration required 'in vitro' makes it unlikely that this xenobiotic could be directly related to human toxicity.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Anilides; Animals; Arachidonic Acid; Enzyme Activation; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Kinetics; Linoleic Acids; Lipoxygenase; Macrophages; Mice; Oils; Peritoneal Cavity