Dietary Iron Repletion Stimulates Hepatic Mobilization of Vitamin A in Previously Iron-Deficient Rats as Determined by Model-Based Compartmental Analysis

Abstract

ABSTRACTBackgroundIron deficiency can result in hyporetinolemia and hepatic vitamin A (VA) sequestration.ObjectivesWe used model-based compartmental analysis to determine the impact of iron repletion on VA metabolism and kinetics in iron-deficient rats.MethodsAt weaning, Sprague-Dawley rats were assigned to either a VA-marginal diet (0.35 mg retinol equivalent/kg) with adequate iron (35 ppm, control group [CN]) or reduced iron (3 ppm, iron-deficient group [ID–]), with an equivalent average body weight for each group. After 5 wk, n = 4 rats from each group were euthanized for baseline measurements of VA and iron indices, and the remaining rats (n = 6 CN, n = 10 ID–) received an intravenous injection of 3H-labeled retinol in an emulsion as tracer to initiate the kinetic study. On day 21 after dosing, half of the ID– rats were switched to the CN diet to initiate iron repletion, referred to as the iron-repletion group (ID+). From the time of dosing, 34 serial blood samples were collected from each rat over a 92-d time course. Plasma tracer and tissue tracee data were fitted to 6- and 4-compartment models, respectively, to analyze the kinetic behavior of VA in all groups.ResultsOur mathematical model indicated that ID– rats exhibited a nearly 6-fold decrease in liver VA secretion and >4-fold reduction in whole-body VA utilization, compared with CN rats, whereas these perturbed kinetic behaviors were notably corrected in ID+ rats, close to those from the CN group.ConclusionsIron repletion can remove the inhibitory effect that iron deficiency exerts on hepatic mobilization of VA and restore retinol kinetic parameters to values similar to that of never-deficient CN rats. Together with improvements in iron and VA indices, our results suggest that restoration of an iron-adequate diet is sufficient to improve VA kinetics after a previous state of iron deficiency.