Common Chelating Agents

    Below are some common chelating agents and their known and proposed mechanisms of action, side-effects, and principle uses.

    EDTA (ethylenediaminetetraacetic acid).  This is a molecule that complexes with divalent or trivalent cations.  One proposed mechanism of action is that at physiologic pH, EDTA complexes with the calcium in artherosclerotic plaques.  It is thought that once the calcium is removed from the plaque, the plaque will dissolve and the patency of the arteries would be restored. A variation of this possible mechanism is that when EDTA binds serum calcium, the calcium from the plaques will be mobilized thus allowing the plaque to dissolve.  Another proposed mechanism is that EDTA binds copper and iron cations and, in turn, effectively stops the chain of reactions that leads to lipid perioxidation which is important in plaque formation.  EDTA is also thought to stop platelet aggregation, relax vascular tone, and lower levels of LDLs and VLDLs.  Side effects of EDTA infusions include burning at the infusion site (reduced by co administering magnesium sulfate), renal toxicity, arrhythmias, dermatitis, myelosuppression, thromboemboli formation, and histamine-like reactions.

    Deferoxamine.  This chelator is used to treat iron toxicity found is certain hematological disorders such as sickle cell anemia and types of thalassemia.  It may act to improve reperfusion injury that sometimes occurs in bypass surgery.  It is proposed that deferoxamine reduces the amount of stored iron in the body, thus there is less iron to react with free radicals produced during transient ischemia.  Free radical are what cause tissue damage, but if they cannot with the iron no damage will result.  Deferoxamine is also being researched as an agent used in the treatment of anthracycline-induced cardiotoxicity.  It has been established protective agent against doxirubicin-induced cardiotoxicity in women receiving doxirubicin for breast cancer.  Side effects include night blindness, optic neuropathy, visual field defects and other ocular problems.  Untoward effects reported also include ototoxicity and effect on the lungs.

    Dexrazoxane is a chelator that has been approved by the FDA to be used to reduce the severity of doxirubicin induced cardiomyopathy in women with metastatic breast cancer who have received more than 300 mg/kg of doxirubicin.   Abnormalities in bone marrow, renal, and hepatic function have been noted.