Trans n-3 eicosapentaenoic and docosahexaenoic acid isomers exhibit different inhibitory effects on arachidonic acid metabolism in human platelets compared to the respective cis fatty acids.
N-3 trans geometrical isomers of 20:5 n-3 and 22:6 n-3 were isolated from rats fed heated linseed oil. The ability of these acids to inhibit 20:4 n-6 metabolism by human platelets was examined. The concentrations required to inhibit 50% of platelet aggregation (IC50) induced by 2.5 microM 20:4 n-6 were higher for the 20:5 delta 17t isomer compared to all cis 20:5 n-3; means 29.2 and 7.6 microM, respectively (P less than 0.05). There were no significant differences in IC50 between 22:6 delta 19t and all cis 22:6 n-3; means 4.3 and 5.6 microM, respectively (P greater than 0.05). Inhibition of action of cyclooxygenase on 20:4 n-6 was similar for 20:5 delta 17t and 20:5 n-3 when examined at their IC50s, but comparison at equal concentrations indicated that 20:5 n-3 was a significantly better inhibitor (P less than 0.05). The ability to inhibit platelet aggregation was paralleled by cyclooxygenase inhibition as determined by thromboxane B2 and 12-hydroxyheptadecatrienoic acid formation. 22:6 delta 19t appeared to inhibit cyclooxygenase more completely than 22:6 n-3, examined at their IC50s or at similar concentrations (P less than 0.05). Isomers of 20:5 n-3 and 22:6 n-3 having an n-3 cis or trans bond appear to have similar modes of action, although levels required for effectiveness are different for the C20 acids.
O'Keefe
S F
SF
INRA, Station de Recherches sur la Qualité des Aliments de l'Homme, Dijon, France.
Lagarde
M
M
Grandgirard
A
A
Sebedio
J L
JL
D001095:Arachidonic Acids / Q000097:blood / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D013237:Stereoisomerism; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D015118:Eicosapentaenoic Acid