TY - JOUR
T1 - Consequences of parenteral iron-dextran loading investigated in minipigs. A new model of transfusional iron overload
AU - Jensen, Peter Diedrich
AU - Nielsen, Asbjoern Haaning
AU - Simonsen, Carsten Wiberg
AU - Baandrup, Ulrik Thorngren
AU - Vyberg, Mogens
AU - Jensen, Svend Eggert
AU - Magnusdottir, Sigridur Olga
AU - Krarup, Henrik Bygum
AU - Nielsen, Michael Festersen
AU - Kjaergaard, Benedict
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Iron dextran
KW - Iron overload
KW - Magnetic resonance imaging
KW - Mini-pig model
KW - Transfusional iron overload
UR - http://www.scopus.com/inward/record.url?scp=85083775266&partnerID=8YFLogxK
U2 - 10.1016/j.bcmd.2020.102440
DO - 10.1016/j.bcmd.2020.102440
M3 - Journal article
C2 - 32353700
AN - SCOPUS:85083775266
SN - 1079-9796
VL - 83
JO - Blood Cells, Molecules and Diseases
JF - Blood Cells, Molecules and Diseases
M1 - 102440
ER -