Iron chelators inhibit human platelet aggregation, thromboxane A2 synthesis and lipoxygenase activity.
The iron chelators desferrioxamine and 1,2-dimethyl-3-hydroxypyrid-4-one (L1) inhibited human platelet aggregation in vitro as well as thromboxane A2 synthesis and conversion of arachidonate to lipoxygenase-derived products. Non-chelating compounds related to L1 were without effect on cyclooxygenase or lipoxygenase activity. Since both cyclooxygenase and lipoxygenase are iron-containing enzymes, it is suggested that the inhibition of platelet function by these iron chelators may be related to the removal or binding of iron associated with these enzymes. These iron chelators may therefore be of potential therapeutic value as platelet antiaggregatory agents and of possible use in the treatment of atherosclerotic and inflammatory joint diseases.
Barradas
M A
MA
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, England.
Jeremy
J Y
JY
Kontoghiorghes
G J
GJ
Mikhailidis
D P
DP
Hoffbrand
A V
AV
Dandona
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008084:Lipoxygenase / Q000097:blood*; D010975:Platelet Aggregation Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011728:Pyridones / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood*
D001095:Arachidonic Acids; D007502:Iron Chelating Agents; D010975:Platelet Aggregation Inhibitors; D011728:Pyridones; D016718:Arachidonic Acid; D000077543:Deferiprone; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D007501:Iron; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D003676:Deferoxamine; D001241:Aspirin; D004837:Epinephrine