Stearidonic acid, an inhibitor of the 5-lipoxygenase pathway. A comparison with timnodonic and dihomogammalinolenic acid.
Leukotrienes have been shown to play an important role as mediators in various disease processes, including asthma and inflammation; thus, their synthesis is tightly regulated. The major precursor of leukotrienes is arachidonic acid (20:4n-6). Fatty acids which are structurally similar to 20:4n-6, such as eicosatrienoic acid (20:3n-6; dihomogammalinolenic acid) and eicosapentaenoic acid (20:5n-3; timnodonic acid) have been found to inhibit leukotriene biosynthesis. Because of the structural similarity of octadecatetraenoic acid (18:4n-3; stearidonic acid) with 20:4n-6, the present study was undertaken to determine whether stearidonic acid also exerts an inhibitory effect on the 5-lipoxygenase pathway. Human leukocytes were incubated with 18:4n-3 (20 microM or 10 microM), 20:5n-3 (20 microM) or 20:3n-6 (20 microM) and subsequently stimulated with 1 microM ionophore A23187 and 20:4n-6 (20 microM or 10 microM). The 5-lipoxygenase products were then measured by high-performance liquid chromatography. Leukotriene synthesis was reduced by 50% with 20 microM 18:4n-3 and by 35% with 10 microM 18:4n-3. Formation of 5S,12S-di-hydroxy-eicosatetraenoic acid and of 5-hydroxy-eicosatetraenoic acid was decreased by 25% with 20 microM 18:4n-3 and by 3% with 10 microM 18:4n-3. The inhibition observed with 20 microM 18:4n-3 appeared to be of the same order as that observed with 20 microM 20:5n-3; the inhibition observed with 18:4n-3 was shown to be dose-dependent. The inhibition produced by 20 microM 20:3n-6 was greater than that observed with either 20 microM 18:4n-3 or with 20 microM 20:5n-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Guichardant
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M
Nestec Ltd., Nestle Research Centre, Lausanne, Switzerland.
Traitler
H
H
Spielmann
D
D
Sprecher
H
H
Finot
P A
PA
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D015289:Leukotrienes / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors
D015525:Fatty Acids, Omega-3; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D000001:Calcimycin; D015118:Eicosapentaenoic Acid; D015126:8,11,14-Eicosatrienoic Acid; C062895:stearidonic acid