title: A Speciation Study on the Perturbing Effects of Iron Chelators on the Homeostasis of Essential Metal Ions.
abstract: A number of reports have appeared in literature calling attention to the depletion of essential metal ions during chelation therapy on β-thalassaemia patients. We present a speciation study to determine how the iron chelators used in therapy interfere with the homeostatic equilibria of essential metal ions. This work includes a thorough analysis of the pharmacokinetic properties of the chelating agents currently in clinical use, of the amounts of iron, copper and zinc available in plasma for chelation, and of all the implied complex formation constants. The results of the study show that a significant amount of essential metal ions is complexed whenever the chelating agent concentration exceeds the amount necessary to coordinate all disposable iron--a frequently occurring situation during chelation therapy. On the contrary, copper and zinc do not interfere with iron chelation, except for a possible influence of copper on iron speciation during deferiprone treatment.
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari, Cagliari, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Crisponi
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari, Cagliari, Italy.
authors.forename: Valeria Marina
authors.initials: VM
authors.lastname: Nurchi
authors.affiliation: Dipartimento di Scienze Chimiche e Geologiche, University of Cagliari, Cagliari, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Crespo-Alonso
authors.affiliation: Dipartimento di Chimica e Farmacia, University of Sassari, Sassari, Italy.
authors.forename: Gavino
authors.initials: G
authors.lastname: Sanna
authors.affiliation: Dipartimento di Chimica e Farmacia, University of Sassari, Sassari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zoroddu
authors.affiliation: Dipartimento di Chimica, University of Pavia, Pavia, Italy.
authors.forename: Giancarla
authors.initials: G
authors.lastname: Alberti
authors.affiliation: Dipartimento di Chimica, University of Pavia, Pavia, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Biesuz
mesh_terms: D003300:Copper / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D000077543:Deferiprone; D003676:Deferoxamine / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007477:Ions / Q000737:chemistry; D007502:Iron Chelating Agents / Q000737:chemistry / Q000627:therapeutic use*; D008670:Metals / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011728:Pyridones / Q000737:chemistry / Q000627:therapeutic use; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000473:pathology
chemical_list: D007477:Ions; D007502:Iron Chelating Agents; D008670:Metals; D011728:Pyridones; D012709:Serum Albumin; D000077543:Deferiprone; D003300:Copper; D003676:Deferoxamine; D015032:Zinc