Interference of some flavonoids and non-steroidal anti-inflammatory drugs with oxidative metabolism of arachidonic acid by human platelets and neutrophils.
The effect of ten flavonoids was studied on the stimulation of washed human platelets by either arachidonic acid or thrombin. The oxygenated metabolites released were analyzed by radioimmunoassay, glass-capillary-column gas chromatography and high-pressure liquid chromatography. No effect was evidenced for naringenin, rutinose and phloridzin up to 1000 microM. Thromboxane B2 and 12-hydroxyeicosatetraenoic acid production was depressed simultaneously by all other compounds at different IC50. When tested for their effect on reversibility, however, cyclooxygenase and lipoxygenase inhibition was found to be different depending upon the flavonoid used. All compounds, except morin and rutin, inhibited platelet aggregation and [14C]serotonin release with parallel inhibition of thromboxane synthesis when tested on arachidonic acid-induced platelet-rich plasma stimulation. Some flavonoids inhibited the metabolism of human neutrophils stimulated by ionophore A23187 as assessed by high-performance liquid chromatography. Our results show that flavonoids interfere with the different oxidative metabolisms of arachidonic acid. No clearcut specificity could be found between one compound and one metabolic pathway.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013917:Thrombin / Q000502:physiology; D013931:Thromboxanes / Q000096:biosynthesis / Q000097:blood
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005419:Flavonoids; D013931:Thromboxanes; D016718:Arachidonic Acid; D013917:Thrombin