Consequences of parenteral iron-dextran loading investigated in minipigs. A new model of transfusional iron overload.

Autor: Jensen PD; Department of Hematology, University Hospital Aalborg, Aalborg, Denmark. Electronic address: d222615@dadlnet.dk., Nielsen AH; Department of Civil Engineering, Aalborg University, Aalborg, Denmark., Simonsen CW; Department of Radiology, Aalborg University, Aalborg, Denmark., Baandrup UT; Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Aalborg University Hospital, Denmark., Vyberg M; Department of Pathology, Aalborg University Hospital, Aalborg, Denmark., Jensen SE; Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark., Magnusdottir SO; Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark., Krarup HB; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark., Nielsen MF; Department of Clinical Medicine and Surgery, Viborg Hospital, Viborg, Denmark., Kjaergaard B; Biomedical Research Laboratory, Aalborg University Hospital, Aalborg, Denmark; Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark.
Jazyk: angličtina
Zdroj: Blood cells, molecules & diseases [Blood Cells Mol Dis] 2020 Jul; Vol. 83, pp. 102440. Date of Electronic Publication: 2020 Apr 19.
DOI: 10.1016/j.bcmd.2020.102440
Abstrakt: Patients with blood transfusion-dependent anemias develop transfusional iron overload (TIO), which may cause cardiosiderosis. In patients with an ineffective erythropoiesis, such as thalassemia major, common transfusion regimes aim at suppression of erythropoiesis and of enteral iron loading. Recent data suggest that maintaining residual, ineffective erythropoiesis may protect from cardiosiderosis. We investigated the common consequences of TIO, including cardiosiderosis, in a minipig model of iron overload with normal erythropoiesis. TIO was mimicked by long-term, weekly iron-dextran injections. Iron-dextran loading for around one year induced very high liver iron concentrations, but extrahepatic iron loading, and iron-induced toxicities were mild and did not include fibrosis. Iron deposits were primarily in reticuloendothelial cells, and parenchymal cardiac iron loading was mild. Compared to non-thalassemic patients with TIO, comparable cardiosiderosis in minipigs required about 4-fold greater body iron loads. It is suggested that this resistance against extrahepatic iron loading and toxicity in minipigs may at least in part be explained by a protective effect of the normal erythropoiesis, and additionally by a larger total iron storage capacity of RES than in patients with TIO. Parenteral iron-dextran loading of minipigs is a promising and feasible large-animal model of iron overload, that may mimic TIO in non-thalassemic patients.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests, and there are no conflicts of interest to disclose.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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