Iron Deficiency

Modeling has also been used to ascertain the most likely mechanism by which iron deficiency alters vitamin A kinetics (Jang et al., 2000). Iron and vitamin A deficiencies often coexist in human populations, and in animal models, iron deficiency is associated with lowered plasma retinol concentrations and increased liver vitamin A levels. We used model-based compartmental analysis to study the effects of iron deficiency on vitamin A metabolism. Kinetic data were compared in control and iron-deficient rats following administration of [3H]retinol-labeled plasma, and the approach applied by Kelley and Green (1998) was used to model the results. As in our previous studies, either a three- or four-compartment model was sufficient to fit plasma tracer data obtained during 48 days after administration of label. Visual inspection of the curves indicated that iron deficiency decreased retinol recycling from the slow turning-over pool(s) to plasma and that fractional irreversible utilization of vitamin A was lower in the iron-deficient animals. The model predicted a decrease in irreversible utilization of vitamin A and a decrease in vitamin A absorption efficiency in iron-deficient rats. The results suggested that liver vitamin A accumulation in iron deficiency might be due to impaired release of the vitamin into plasma and imply that decreased vitamin A mobilization from liver might account for the lower plasma retinol pool size. It is possible that the same enzyme that causes the increased mobilization of retinol in TCDD-treated rats is inhibited by iron deficiency.

Data from the TCDD and iron studies have also been analyzed using nonsteady state compartmental analysis (Green and Green, 2003) to reflect the fact that, in both cases, the vitamin A system was not actually in a steady state. Starting from the steady state solution, we developed a parallel model for tracee and set the model parameters [L(I,J)s; Table I] equal in the tracer and tracee models. Then we looked for minimal changes in the steady state model that would accurately describe the changes in liver vitamin A levels in iron-deficient or TCDD-treated rats. In both cases, we found that, by making time variant the one model parameter related to mobilization of liver vitamin A stores, we could account for the changes in liver vitamin A. The rate of retinol mobilization was held constant at a different value in the two models in order to maintain homeostasis of the plasma retinol pool and the two other non-liver pools of vitamin A. In iron deficiency, liver vitamin A levels increased with time whereas with TCDD treatment, levels decreased with time. These analyses emphasize the added information about both tracer and tracee that can be gained through a nonsteady state model.

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