Selective conjugated fatty acids inhibit guinea pig platelet aggregation.
Conjugated linoleic acids have been shown to reduce eicosanoid release from select tissues and/or cells. To elucidate effects of conjugated linoleic acid isomers on cyclooxygenase-1 (COX-1) activity and their application as platelet aggregation inhibitors, conjugated linoleic acid isomers and conjugated nonadecadienoic acid were incubated with ovine COX-1 and Raw264.7 macrophage to examine their effects on COX-1 activity. The effects were further examined in collagen and ADP-induced guinea pig whole blood platelet aggregation. Fatty acids tested were shown to inhibit COX-1 enzymatic activity. However, only 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid inhibited collagen and ADP-induced platelet aggregation with IC(50) 125.9 microM (74.2 microM to 213.4 microM, 95% confidence interval), 99.3 microM (52.8 microM to 187.2 microM, 95% confidence interval) and 124.3 microM (85.1 microM to 181.5 microM, 95% confidence interval) respectively in collagen-induced aggregation. TxB(2) release was also appreciably inhibited by 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid. Based on these data, we conclude 10t, 12c-conjugated linoleic acid, 9t, 11t-conjugated linoleic acid and conjugated nonadecadienoic acid are platelet aggregation inhibitors while 9c, 11t-conjugated linoleic acid is a moderate inhibitor and linoleic acid, and 9c, 11c-conjugated linoleic acid have no effect on whole blood platelet aggregation.
Li
Guangming
G
Molecular and Environmental Toxicology, University of Wisconsin-Madison, 53706, USA.
Butz
Daniel
D
Dong
Baiyan
B
Park
Yeonhwa
Y
Pariza
Michael W
MW
Cook
Mark E
ME
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D006168:Guinea Pigs; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D051545:Cyclooxygenase 1