title: Deferiprone therapy in homozygous human beta-thalassemia removes erythrocyte membrane free iron and reduces KCl cotransport activity.
abstract: Deposition of free iron is a characteristic feature of beta-thalassemia (beta-thal) red blood cells believed to play an important role in the generation of oxidative injury to the cell membrane. Increased red blood cell KCI cotransport, reduced K content, and cell dehydration are also found in beta-thal red blood cells. It is not known, however, whether deposition of free iron plays a role in these membrane transport changes. To explore this issue, we studied-both in vitro and in vivo-the effect on KCI cotransport of removing red blood cell membrane free iron from beta-thal erythrocytes. Eleven patients with beta-thal major who underwent long-term transfusion and were treated with deferiprone (75 mg/kg/day) for 9 months participated in the study. Deferiprone therapy removed membrane free iron from beta-thal erythrocytes, which was followed by reduced KCI cotransport activity. The reduced KCI cotransport activity was accompanied by an increase in the red blood cell K content. These data suggest that the increased activity of KCI cotransport in beta-thal red blood cells is mediated by the deposition of membrane free iron, a mechanism that may be attenuated by deferiprone therapy.
authors.affiliation: Department of Internal Medicine, University of Verona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: de Franceschi
authors.forename: O
authors.initials: O
authors.lastname: Shalev
authors.forename: A
authors.initials: A
authors.lastname: Piga
authors.forename: M
authors.initials: M
authors.lastname: Collell
authors.forename: O
authors.initials: O
authors.lastname: Olivieri
authors.forename: R
authors.initials: R
authors.lastname: Corrocher
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism*; D002648:Child; D002712:Chlorides / Q000378:metabolism; D000077543:Deferiprone; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D011188:Potassium / Q000378:metabolism; D011728:Pyridones / Q000627:therapeutic use*; D028021:Sodium-Potassium-Chloride Symporters; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002712:Chlorides; D007502:Iron Chelating Agents; D011728:Pyridones; D028021:Sodium-Potassium-Chloride Symporters; D000077543:Deferiprone; D007501:Iron; D011188:Potassium