Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans

Abstract

Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of 59Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous 59Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40). Mean mucosal iron uptake and mucosal iron transfer (±SD) were elevated in patients with HH (59 ± 18%, 80 ± 15% respectively), HA (65 ± 17%, 74 ± 18%) and ID (84 ± 14%, 94 ± 6%) compared to healthy controls (43 ± 19%, 64 ± 18%) (p < 0.05) resulting in increased iron retention after 14 days compared to healthy controls in all groups (p < 0.01). The fraction of retained iron utilized for red cell production was 0.37 ± 0.17 in untreated HA, 0.55 ± 0.20 in untreated HH and 0.99 ± 0.22 in ID (p < 0.01). Interestingly, compared to red blood cell iron utilization after oral iron administration, red blood cell iron utilization was higher after injection of transferrin-bound iron in HA and HH. Liver iron retention was considerably higher in HH and HA compared to ID. We hypothesize that albumin serves as a scavenger of absorbed Fe(II) for delivering albumin-bound Fe(III) to hepatocytes.

A Rationally Designed Complex Replenishes the Transferrin Iron Pool Directly and with High Specificity

“…For this reason, we opted to treat IRIDA in Tmprss 6 knockout through a series of multiple repeated small doses of Fe, rather than fewer large doses. The serum half-life of transferrin-Fe in iron-deficient humans is reported to be ∼50 min, whereas based on dose-conversion principles, we estimate that the Fe-BBG elimination half-life in humans will be longer by over an order of magnitude . In other words, we expect a substantially larger fraction of the injected Fe to be absorbed by humans receiving an equivalent dose of Fe-BBG.…”

Di-(2-ethylhexyl) phthalate exposure induces liver injury by promoting ferroptosis via downregulation of GPX4 in pregnant mice

“…It has been reported that defects in Tfr1 cause systemic iron overload and hemochromatosis through downregulation of hepcidin ( Kawabata, 2019 ). Therefore, the determination of iron accumulation is crucial in diagnosing the occurrence and progression of many liver and iron-related diseases ( van Vuren et al, 2020 ). In this study, consistent with previous findings, we found that iron accumulated and elevated the Fe 2+ concentration in liver tissue, and MDA, as one of the final products of lipid peroxidation in cell membranes, was significantly increased.…”