Dataset Information

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis.

ABSTRACT: Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Deferasirox in iron overloaded osteoclasts from thalassemic patients and donors measuring intracellular iron, TRAP expression and osteoclast activity. We confirmed ELT iron chelation capacity also in bone tissue and a synergic effect when used with Deferasirox. Moreover, having demonstrated its effects on osteoclast activity, we suggest for the first time that ELT could ameliorate bone tissue's health reducing bone mass loss.

SUBMITTER: Punzo F

PROVIDER: S-EPMC6277068 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis.

Punzo Francesca F Tortora Chiara C Argenziano Maura M Casale Maddalena M Perrotta Silverio S Rossi Francesca F

PloS one 20181203 12

Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Def ...[more]

PMID: 30507954

Similar Datasets

Project description:In iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low-molecular-weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate (R(2)*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron-chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate (R(2)), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the 'reduced transverse relaxation rate' (RR(2)), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR(2) could detect changes produced by 1 week of iron-chelating therapy in patients with transfusion-dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid-ventricular short-axis planes of the heart, initially after suspending iron-chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron-chelating therapy, significant decreases were observed in the mean myocardial RR(2) (7.8%, p < 0.01) and R(2) (5.5%, p < 0.05), but not in R(2)* (1.7%, p > 0.90). Although the difference between changes in RR(2) and R(2) was not significant (p > 0.3), RR(2) was consistently more sensitive than R(2) (and R(2)*) to the resumption of iron-chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR(2) may be a promising investigational method for the rapid assessment of the effects of iron-chelating therapy in the heart.

Dataset Information

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis.

Publications

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets