The effect of some flavone drugs on the conversion of prostacyclin to 6-oxoprostaglandin E1.
Flavonoid drugs (rutin, naringenin and quercetin) were compared with indomethacin and sulphasalazine as inhibitors of rat and rabbit renal 9-hydroxyprostaglandin dehydrogenase, prostaglandin synthesis (bovine seminal vesicle microsomes) and inactivation (rabbit colon 100,000 g supernatant), vascular PGI2 formation (rat aortic rings) and for effects on platelet aggregation and on the isolated rat stomach strip. Rutin and naringenin potently inhibited rabbit renal conversion of PGI2 and PGF2 alpha to 6-oxoPGE1 and PGE2, respectively, but had no effect on rat renal 9-hydroxyprostaglandin dehydrogenase activity, prostaglandin breakdown, vascular PGI2 synthesis, platelet aggregation or the anti-aggregatory effect of PGI2 and 6-oxoPGE1. High concentrations (100 microM) of both drugs inhibited the spasmogenic effect of PGI2 on the rat stomach strip. Naringenin and quercetin (1 mM) inhibited whilst rutin (1 mM) stimulated microsomal prostaglandin synthesis. These results suggest that rutin and naringenin may be useful experimental tools to study the biological roles of 6-oxoPGE1.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002417:Cattle; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000378:metabolism*; D011817:Rabbits; D012669:Seminal Vesicles / Q000378:metabolism; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D005419:Flavonoids; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; C022950:6-ketoprostaglandin E1; D015237:Dinoprost; D011464:Epoprostenol; D000527:Alprostadil; D015232:Dinoprostone