Dietary vitamin A and iron metabolism in the rat.

The experiments presented in this thesis were carried out to simulate the interrelationship between vitamin A and iron metabolism, which has been illustrated in human studies in third world countries and to elucidate underlying mechanisms.Effects of manipulation with dietary vitamin A on vitamin A and iron status were studied in rats. Recurrent effects on iron metabolism with moderate vitamin A deficiency were: iron accumulation in spleen and bone; reduction in total ironbinding capacity, a measure of transferrin and reduced total liver iron, caused by a reduction in liver weight. These effects were reversed by vitamin A supplementation for 10-12 days. Mild vitamin A deficiency produced anaemia followed by increased iron absorption. When vitamin A status further deteriorated, haemoglobin concentrations rose, due to haemoconcentration. Rats with chronic vitamin A deficiency may be less affected by haemoconcentration. But there was no anaemia in mature female rats with stable low plasma retinol levels.As to the mechanism by which vitamin A might influence iron metabolism, we have speculated that with vitamin A deficiency, blood cell synthesis is impaired, leading to increased destruction of malformed red blood cells and increased iron stores in the macrophages of bone marrow and spleen. In addition synthesis of transferrin might be impaired, possibly at the level of transferrin glycosylation. These hypotheses could not be confirmed by measuring transferrin glycosylation and indicators of red blood cell synthesis and breakdown in rats fed diets deficient in vitamin A.Alternatively, transferrin synthesis might be regulated by vitamin A at the level of gene transcription. With the use of a gene bank, candidate retinoic acid response elements for transferrin and erythropoietin were located. However, it was not possible to confirm a role for vitamin A in transferrin gene transcription by using cultured liver cells incubated with all- trans and 9- cis retinoic acid.Finally, evaluating the rat as animal model it can be deducted from these studies that for optimal standardization of experiments with young growing rats involving nutrients such as vitamin A and iron, diets fed to their dams should also be defined and controlled