Induction of Dietary Iron Deficiency in Rhesus Monkeys: Sequential Changes in Serum Ferritin and Other Biochemical Indicators of Iron Status

Abstract

The usefulness of serum ferritin as a measure of subclinical stages of iron deficiency has been tested in monkeys by inducing a mild iron deficiency dietarily over a period of 12 months. Various biochemical indicators of iron status were measured periodically along with analysis of liver iron and iron staining of bone marrow samples obtained by biopsy, at the end of the experiment. A mild form of iron deficiency was confirmed by bone marrow staining for iron. Of all the biochemical indicators tested, significant decreases were seen in hemoglobin and hematocrit at the 11th and 10th months, respectively. These changes were consistent with the changes later found in bone marrow grading for iron. Serum ferritin concentration and liver iron concentration did not show any significant difference between the controls and iron-deficient monkeys. Thus, these results do not support the existence of a latent stage of iron deficiency. In the mild form of iron deficiency, the functional compartment, represented by bone marrow iron and hemoglobin, is sensitive to depletion even when there were no changes in storage compartment represented by liver iron and serum ferritin.

Changes in Biochemical Indicators of Iron Status during Iron Repletion and Depletion in Monkeys

“…In contrast, we have dem onstrated that serum ferritin concentration is not a reliable measure of mild iron depiction in monkeys [5]. But in this study both liver iron content and serum ferritin were not al tered in any group other than group 4, which showed a tenfold increase in the accumulation of liver nonheme iron.…”

“…Previously, we have shown that feeding of an iron-deficient diet for a period of 12 months produced a mild iron deficiency in monkeys [5]. The data obtained at the end of 12 months that were considered as the initial values for the present study arc presented in table 1 along with the initial and final body weight, bone marrow grading and liver iron of the subgroups.…”

“…Study Design A group of 12 rhesus monkeys (Macaca midaita) which were subjected to dietary iron deficiency over a period of l year along with 6 control animals were uti lized for this study [5], The animals were randomly subdivided into different treatment groups. The exper imental design, the mode of iron depletion-repletion and the initial hematological and bone marrow grading of the animals are given in table l. The control animals were subdivided into 2 groups (groups l and 2) and received an iron-depleted diet.…”

“…The method involves the use of partially purified polyclonal antibody in rabbit raised against purified monkey liver ferritin [7] for coating the plate and horseradish peroxidase-conjugate of a similar antibody in another rabbit as indicator. The assay conditions adopted were similar to that described in detail earlier [5] with a within-assay coef ficient of variation less than 5% and a day-to-day vari ability of less than 10%.…”

“…In our previous studies, we have addressed the question whether the serum level of ferri tin is a reliable index of small changes in iron stores, using the monkey model [5], Monitor ing the sequential changes over l year indi cated that the circulating ferritin concentra tion did not reflect the changes occurring in iron status during mild forms of iron deficien cy. Significant changes in the expected direc tion were seen only in hematological parame ters like hemoglobin and hematocrit.…”