title: Influence of fatty acid anilides present in toxic oils on the metabolism of exogenous arachidonic acid in cultured human endothelial cells.
abstract: The effect of fatty acid anilides (FAA) on the exogenous arachidonic acid (AA) metabolism and toxicity of isolated human endothelial cells was studied to clarify their possible role in the etiology of toxic oil syndrome. Confluent cells were incubated with and without linoleic acid anilide (LAA), oleic acid anilide (OAA) and two unrelated samples for 2-24 h prior to the addition of [l-14C]AA alone or with calcium ionophore A-23187. The eicosanoids produced were analyzed by RP-HPLC. A dual stimulatory and inhibitory effect on the conversion of exogenous AA as a function of preincubation time with anilides (100 and 1000 microM) was observed. Treated cells significantly increased (1-3-fold) the production of the main cyclooxygenase-derived prostanoids (6-keto-PGF1 alpha and PGF2 alpha) formed by these cells, with a maximum stimulatory effect after 2-3 h, only when AA was used alone. However, afterwards a time- and dose-dependent decrease in prostanoid formation was observed with LAA (P < 0.05 at 24 h), either in the absence or presence of ionophore A-23187 in the incubation mixture. This inhibitory effect on cyclooxygenase was not observed with OAA, which still stimulate after 24 h of treatment. The changes in prostanoid synthesis were not followed with a parallel release in the lactate dehydrogenase activity in the medium (except with unrelated samples). Moreover, anilide treatment increased the appearance of cytosolic lipid droplets or vacuoles after 2 and 5 h of contact with LAA and OAA, respectively. From these results, it was suggested that anilides impair prostanoid synthesis in endothelial cells; their stimulatory effect could be explained by an unspecific effect on cell membrane, not related to cell toxicity and the inhibitory effect by an inhibition of the cyclooxygenase activity. These observations further contribute to our understanding of the possible role of anilides in the etiology of the toxic oil syndrome.
authors.affiliation: Atherothromhosis-Vascular Biology Dept., Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Pich
authors.forename: S
authors.initials: S
authors.lastname: López
authors.forename: L
authors.initials: L
authors.lastname: Vila
authors.forename: C
authors.initials: C
authors.lastname: Lagunas
authors.forename: C
authors.initials: C
authors.lastname: de Castellarnau
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000032:analysis / Q000378:metabolism*; D001937:Brassica; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008041:Linoleic Acids / Q000494:pharmacology*; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology; D009829:Oleic Acids / Q000494:pharmacology*; D010169:Palmitic Acids / Q000494:pharmacology; D010938:Plant Oils / Q000506:poisoning; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D011453:Prostaglandins / Q000032:analysis; D000074262:Rapeseed Oil; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000813:Anilides; D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D005229:Fatty Acids, Monounsaturated; D008041:Linoleic Acids; D009227:Myristic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D010938:Plant Oils; D011453:Prostaglandins; D000074262:Rapeseed Oil; D019814:Myristic Acid; C039294:linoleylanilide; C038731:oleoylanilide; D007770:L-Lactate Dehydrogenase; D011451:Prostaglandin-Endoperoxide Synthases