1985 Volume 13 Issue 4 Pages 825-829
Arachidonic acid (AA) is well known to be metabolized to thromboxane (TX) A2, 12-hydroxyheptadecatrienoic acid (HHT) and 12-hydroxyeicosatetraenoic acid (12-HETE) in platelets. Prostaglandin endoperoxides and TXA2 are known to be potent aggregating agents. On the otherr hand, the labile 12-lipoxygenase metabolite, 12-hydroperoxyeicosatetraenoic acid (12-HPETE) has been reported to have a rather anti-aggregating action.
It has been reported that eicosapentaenoic acid (EPA) has a potent inhibitory effect on platelet aggregation. TXA3 produced from EPA is nonaggregating agent. Although major metabolites of EPA in platelets is said to be those of 12-lipoxygenase pathway, the effect of them has not been clearly elucidated yet. So, we examined the effect of 12-lipoxygenase metabolites of EPA on platelet function and compared them with those of AA.
Both of the labile 12-lipoxygenase metabolites, 12-HPETE and 12-hydroperoxyeicosapentaenoic acid (12-HPEPE) suppressed dose-dependently platelet aggregation and release of 5-hydroxytryptamine (5-HT) induced by collagen and AA, while 12-HETE and 12-hydroxyeicosapentaenoic acid (12-HEPE) had no such effects. The inhibitory effects of these 12-hydroperoxy compounds on platelet aggregation and release reaction seem to be almost equipotent. However, 5- and 15-hydroperoxy isomers were less potent in inhibiting aggregation.
These results may indicate that 12-HPETE and 12-HPEPE have a potent anti-aggregatory activity and may play a role in regulating platelet aggregability.
