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Clofibric Acid, A Peroxisome Proliferator-Activated Receptor Alpha Agonist, forms a Ternary Complex with the Ferric Iron

It has been proposed that the antihypelipidemic and antihypercholesteremic effect of fibrates is a result of activating the peroxisome proliferator-activated receptor alpha (PPARα), leading to the enhancement of lipid catabolism. Since high iron status has been linked to the increased risk of heart disease, and oxidative stress has been implicated in the etiology of atherosclerosis, this study was undertaken to investigate whether prototypic fibrate, clofibric acid (CA) complexes with ferric iron (Fe3+) and determine the nature of the formed iron complexes. Elemental analysis, potentiometric titrations, UV-Vis absorption spectroscopy and ICPMS show that CA binds Fe3+, form a ternary complex, in aqueous solutions at 25ºC. Because CA complexes with copper and prevents copperinduced oxidation reactions and iron chelators blocked ironinduced inflammatory responses, we propose that binding iron by fibrates may contribute to the antiatherogenic effect of these drugs. Binding iron may also be responsible for anemia reported in patients receiving members of this class of PPARα agonists.


Yahia Z Hamada, Samid Rehan, Jasmine Scott

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