Aspirin inhibits platelet 12-hydroxy-eicosatetraenoic acid formation.
The effects of aspirin on platelet 12-hydroxyeicosatetraenoic acid (12-HETE) formation were studied after administration to humans in platelet-rich plasma (PRP) and in vitro in human PRP and in washed platelets (WPs). Healthy volunteers were given orally either single or repeated (1 week) daily doses (20 and 500 mg) of aspirin. Two hours after a single 20 mg aspirin dose, 12-HETE formation by PRP was significantly inhibited. With the highest aspirin dose used (500 mg), the inhibition of 12-HETE formation was more pronounced and long lasting. Thromboxane B2 (TXB2) synthesis was significantly inhibited at 2 hours with the lowest dose. At the 500 mg dose, platelet aggregation was significantly reduced, and TXB2 formation was almost completely suppressed for at least 24 hours. The degree of inhibition of 12-HETE formation at 2 hours after 1 week of daily treatment (20 and 500 mg) was similar to that achieved at 2 hours after the single dose. As far as TXB2 and platelet aggregation are concerned, the effect of 20 mg aspirin was cumulative. In vitro studies show that aspirin (0.25 to 3 mmol/L concentration) significantly inhibits 12-HETE formation in PRP, but not in WPs, suggesting that plasma is required for the aspirin effect on lipoxygenase products. These results indicate that aspirin, even at low doses, not only affects the platelet cyclooxygenase activity but also exerts reversible inhibition of 12-HETE formation, both in vitro and ex vivo. These data may help to further elucidate the role of hydroxyacids in the anti-inflammatory and antipyretic action of aspirin.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D003864:Depression, Chemical; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D013929:Thromboxane B2 / Q000096:biosynthesis
D006893:Hydroxyeicosatetraenoic Acids; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003094:Collagen; D001241:Aspirin