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Ferroportin inhibition attenuates plasma iron, oxidant stress, and renal injury following red blood cell transfusion in guinea pigs
Author(s) -
Baek Jin Hyen,
Shin Hye Kyung H.,
Gao Yamei,
Buehler Paul W.
Publication year - 2020
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.15720
Subject(s) - spleen , medicine , ferroportin , kidney , red blood cell , hemoglobin , pharmacology , blood transfusion , immunology , oxidative stress , hepcidin , inflammation
BACKGROUND Red blood cell (RBC) transfusions result in the sequestration and metabolism of storage‐damaged RBCs within the spleen and liver. These events are followed by increased plasma iron concentrations that can contribute to oxidant stress and cellular injury. We hypothesized that administration of a ferroportin inhibitor (FPN‐INH) immediately after acute RBC exchange transfusion could attenuate posttransfusion circulatory compartment iron exposure, by retaining iron in spleen and hepatic macrophages. STUDY DESIGN AND METHODS Donor guinea pig blood was leukoreduced, and RBCs were preserved at 4°C. Recipient guinea pigs (n = 5/group) were exchange transfused with donor RBCs after refrigerator preservation and dosed intravenously with a small‐molecule FPN‐INH. Groups included transfusion with vehicle (saline), 5 mg/kg or 25 mg/kg FPN‐INH. A time course of RBC morphology, plasma non–transferrin‐bound iron (NTBI) and plasma hemoglobin (Hb) were evaluated. End‐study spleen, liver, and kidney organ iron levels, as well as renal tissue oxidation and injury, were measured acutely (24‐hr after transfusion). RESULTS RBC transfusion increased plasma NTBI, with maximal concentrations occurring 8 hours after transfusion. Posttransfusion iron accumulation resulted in tubule oxidation and acute kidney injury. FPN inhibition increased spleen and liver parenchymal/macrophage iron accumulation, but attenuated plasma NTBI, and subsequent renal tissue oxidation/injury. CONCLUSION In situations of acute RBC transfusion, minimizing circulatory NTBI exposure by FPN inhibition may attenuate organ‐specific adverse consequences of iron exposure.