title: Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator.
abstract: Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and beta-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 microM (mean +/- SEM, 3.1 +/- 0.2 microM) and the percent transferrin (Tf) saturation more than 85 (111 +/- 6), whereas only in 4% of sera were the LPI levels more than 0.4 microM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 +/- 0.5 and 5.4 +/- 0.6 microM to steady mean levels of 2.18 +/- 0.24 and 2.81 +/- 0.14 microM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t(1/2)) of 2 to 3 months. Serum ferritin and red cell membrane-associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t(1/2) of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
authors.affiliation: Thalassaemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakornpathom, Thailand.
authors.forename: Pensri
authors.initials: P
authors.lastname: Pootrakul
authors.forename: William
authors.initials: W
authors.lastname: Breuer
authors.forename: Matias
authors.initials: M
authors.lastname: Sametband
authors.forename: Pornpan
authors.initials: P
authors.lastname: Sirankapracha
authors.forename: Chaim
authors.initials: C
authors.lastname: Hershko
authors.forename: Z Ioav
authors.initials: ZI
authors.lastname: Cabantchik
mesh_terms: D015415:Biomarkers; D000077543:Deferiprone; D004910:Erythrocyte Membrane / Q000378:metabolism; D005500:Follow-Up Studies; D006446:Hemoglobin E; D006801:Humans; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy*; D010084:Oxidation-Reduction; D011237:Predictive Value of Tests; D011728:Pyridones / Q000627:therapeutic use*; D014168:Transferrin / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D015415:Biomarkers; D007502:Iron Chelating Agents; D011728:Pyridones; D014168:Transferrin; D000077543:Deferiprone; D006446:Hemoglobin E; D007501:Iron