Effects of ω-3 Polyunsaturated Fatty Acids, ω-3 Eicosapentaenoic Acid on Prostaglandin Metabolism in Platelets and in Vessel Walls

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It has been reported that ω-3 polyunsaturated fatty acids, especially ω-3 eicosapentaenoic acid (ω-3, EPA), is a potent antagonist of platelet aggregation and therefore might reduce thrombotic disorders. In order to clarify the effect of ω-3 polyunsaturated fatty acids or EPA on the metabolism of prostaglandins and thromboxanes in platelets and vessel wanes, the present study was performed. Highly purified (75%) EPA ethyl ester prepared from sardine fish oil was given to male wister rats (60mg/kg/day for 8 weeks). Plasma EPA concentration and EPA/AA ratio were higher in EPAEE fed rats than in control rats. Platelet aggregability in the rats fed EPAEE was significantly reduced. The generation activity of PGI2 like substance from thoracic aorta of EPA fedrats was markedly higher than that from control rats. The conversion from 14C-arachidonic acid (AA) to 14C-6keto PGF1α was higher in EPA fed rats, but not significant. There was no detectableconversion of 14C-EPA to 14C-17δ-6keto PGF1α, both in EPA fed rat and in control rats. PGI2 like substance generated from aorta of EPA fed rats was thought to be PGI2 itself. EPA rich fish oil concentrate prepared form sardine fish oil was given to 8 healthy male volunteers (1.4g EPA/day, for 4 weeks). EPA concentration both in plasma and platelet were significantly increased after 4 weeks ingestion of fish oil concentrate. Platelet aggregation induced by collagen and threshold dose of ADP were also significantly decreased. Conversion of both 14C-AA to 14C-TXB2 and 14C-EPA to 14C-TXB3 by washed human platelet were not changed during the experiment. The value of the conversion of 14C-EPA to TXB3 was far lower than that of 14C-AA to 14C-TX132T. here was no detectable formation of 14C-TXB3 from 14C-EPAlabeled platelet under the stimulation of collagen, while 14C-EPA was released from the platelet. TXB2 formation from 14C-AA labeled platelet stimulated by collagen was significantly decreased after 4 weeks ingestion of fish oil concentrate. However the conversion of AA released from 14C-AA labeled platelet to TXB2 was not changed during the experiment. On the other hand, the release of AA from 14C-AA labeled platelet was significantly reduced after the experiment. These results indicate that the anti-thrombotic action of EPA and related compounds might be partialy explained by the enhancement of PGI2 production from vessel wall and the reduction of TXA2 formation from platelet due to the reduced generation of AA from platelet membrane.

Effects of ω-3 Polyunsaturated Fatty Acids, ω-3 Eicosapentaenoic Acid on Prostaglandin Metabolism in Platelets and in Vessel Walls

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