Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat.

We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus.

Influence of nutritional iron deficiency development on some aspects of iron, copper and zinc metabolism.

This paper examines the development of iron (Fe) deficiency and its possible interactions with trace elements such as zinc (Zn) and copper (Cu) by investigating iron-deficient and control rats. The effects of iron deficiency were studied at day 0, 10, 20, 30 and 40 in rats fed on an iron-free diet (diet ID). It was found that the critical period in the development of nutritional iron deficiency occurs after 30 to 40 days without iron supplementation. At this time the organism is unable to maintain haemoglobin levels without endangering the iron-dependent enzymatic groups which are essential for life. It was also demonstrated that in a situation of iron deficiency, there occurs a greater absorption of copper, while that of zinc remains unchanged. As iron deficiency progresses, the levels of copper in the spleen and the sternum increase. It is apparent that iron deficiency provokes more marked alterations in the metabolism of copper than of zinc.

Iron-manganese interactions in the evolution of iron deficiency.

This article examines the evolution of nutritional iron deficiency and the possible interactions with other minerals, such as manganese, in control and iron-deficient rats. The evolution of iron deficiency was studied at 0, 10, 20, 30 and 40 days of providing the animals with an iron-free diet (diet 0). It was found that the critical period in the development of nutritional iron deficiency occurs after 30-40 days without iron, at which moment the organism is unable to maintain hemoglobin levels without endangering the iron-dependent enzymatic groups which, in turn, are essential for life. It was also demonstrated that in a situation of iron deficiency, there occurs a greater absorption of manganese. It should be noted that this greater absorption of manganese is not reflected in the concentration of the mineral in the organs. Therefore, it is evident that the interactions of iron with manganese take place at the digestive level with no apparent consequences being observed at the metabolic level.

The absorption of iron, calcium, phosphorus, magnesium, copper and zinc in the jejunum-ileum of control and iron-deficient rats.

The effects of iron deficiency on the absorption of different dietary sources of iron were studied, together with the interactions between iron, calcium, phosphorus, magnesium, copper and zinc in the jejunum-ileum of control and iron-deficient rats. In this study, three perfusion solutions containing different iron sources: ferric citrate, haemoglobin, and equal parts of ferric citrate and haemoglobin were used. In addition, the same perfusion solutions were used with and without 2,4-dinitrophenol, an inhibitor of oxidative phosphorylation. Iron absorption in anaemic rats was greater than in the controls, except after perfusion with solutions containing haemoglobin. The absorption of calcium, copper and zinc in iron-deficient animals was not significantly affected, while the absorption of phosphorus and magnesium increased, with respect to animals in the control group. After perfusion with solutions containing haemoglobin, the absorption values of calcium, copper and zinc were lower than after ferric citrate in both groups (control and iron-deficient rats).

Effect of source of iron on duodenal absorption of iron, calcium, phosphorous, magnesium, copper and zinc in rats with ferropoenic anaemia.

We studied the effects of iron deficiency on the in vivo absorption (by using the intestinal perfusion technique in the duodenum) of different dietary sources of iron (haem, non-haem and equal parts of both forms) and investigated the interactions between iron and calcium, phosphorous, magnesium, copper and zinc in control and iron-deficient rats. Three perfusion solutions containing a different source of iron were used: solution 1, ferric citrate; solution 2, haemoglobin; solution 3, equal parts of ferric citrate and haemoglobin. We also tested the same perfusion solution with 2,4-dinitrophenol (2,4-DNP), an inhibitor or oxidative phosphorylation (solutions 1-I, 2-I and 3-I). In control rats we observed three mechanisms of iron absorption: passive for soluble iron salts, active receptor-mediated for non-haem iron complexes, and active receptor-mediated for haem iron. In anaemic rats iron absorption was greater than in controls, except after perfusion with solution 2 (containing haemoglobin). Absorption increased as a result of both the passive and active, receptor-mediated mechanism for non-haem iron complexes. The active component was influenced by the depletion of haem receptors under severe iron deficiency. The absorption of calcium, copper and zinc in iron-deficient animals was lower than in controls, whereas phosphorus and magnesium absorption were not significantly affected. After perfusion with solution 2 or 3, calcium, copper and zinc absorption were lower than after solution 1. We conclude that ferropoenic anaemia in the rat impairs the absorptive process of those minerals that are absorbed, at the duodenal level mainly via active transport (haem iron, calcium, copper and zinc), but does not affect the active component involved in non-haem iron absorption.

Effects of iron replenishment on iron, calcium, phosphorus and magnesium metabolism in iron-deficient rats.

We investigated the effect of Fe deficiency on the nutritive utilization of Fe, Ca, P and Mg in rats. Aside from the well known depletion of Fe in liver, femur and sternum with low values of Hb, Fe deficiency impaired Ca, P and Mg metabolism at different degrees. Iron deficiency altered Mg absorption, lowered the concentration of Ca in the liver, femur and sternum, raised the concentration of P and Mg in the liver, and decreased P in the femur. The altered status was not completely rectified by iron supplementation as the animals were still slightly anemic at the end of the study. The second purpose of the study was to evaluate the ability of three iron compounds (ferric citrate, ferrous sulfate and ferrous ascorbate) to correct the undesirable effects of Fe deficiency. Ten days after treatment with these diets, Fe-deficient rats still had reduced Mg absorption, especially those fed ferric citrate. The concentrations of hemoglobin approached normal values in all groups; however, serum Fe remained low, indicating that Fe reserves were still depleted. Hepatic and femoral Fe concentrations were also lower in all Fe-deficient groups regardless of the diet given, compared with their respective controls, whereas Fe concentrations in the sternum increased significantly with all three diets, suggesting an increase in erythropoiesis. The concentration of Ca, P and Mg in liver approached normal values, and appeared to normalize in the femur, except that Ca and P concentrations remained low with the citrate diet. In the sternum, a site assumed to have higher requirements for these minerals, the concentrations of Ca, P and Mg also increased. These findings indicate that Fe is involved in the bone mineralization, and that in physiological terms, Fe interacts favorably with Ca, P and Mg metabolism, since Fe deficiency altered the status of these metals. These findings also suggest that ferrous ascorbate and ferrous sulfate were more effectively absorbed than was ferric citrate.

Supplementation of a cereal-milk formula with haem iron palliates the adverse effects of iron deficiency on calcium and magnesium metabolism in rats.

Aside from the well known alteration of Fe status in Fe deficiency, this condition has also a negative effect on the bioavailability of Ca and Mg. We studied the influence of the supplementation of a commercial cereal-milk formula with bovine blood on Fe, Ca, P, and Mg metabolism in control and Fe-deficient rats to investigate whether high Fe levels in diet produce some interactions and the possibility of decreasing these latter by a haem-Fe supplementation. The bioavailability in control and Fe-deficient animals was determined as the apparent digestibility coefficient and hemoglobin regeneration efficiency, both of which are accurate estimations of total Fe utilization. Non-fortified cereal-milk formula decreased the apparent digestibility coefficient of Ca and Mg in Fe-deficient rats; the concentrations of these minerals in liver, femur, and sternum were lower than in control animals. However, when the Fe content of the cereal-milk formula was doubled by supplementation with bovine blood, the adverse effects on the digestive utilization of Ca, and especially of Mg, were palliated, the concentration of these two minerals in the organs investigated increased, and the overall Fe status improved in Fe-deficient rats.

Effects of intestinal resection, cholecalciferol and ascorbic acid on iron metabolism in rats.

The effect of dietary supplementation with ascorbic acid or cholecalciferol on Fe utilization was studied using the metabolic balance technique, in rats in which 50% of the distal small intestine was removed, or in which the mid small intestine was transected and reanastomosed (controls). Three different diets were used. The first (basal diet) contained (g/kg dry wt): protein (casein + 50 mg D,L-methionine/g) 120 and fat (medium-chain triacylglycerols, olive oil and sunflower oil, in equal parts) 40. The other diets were obtained by adding ascorbic acid (150 mg/kg diet) or cholecalciferol (0.4 mg/kg diet) to the basal diet. Apparent digestibility coefficient (ADC) and Fe retention were significantly lower in resected animals than in their respective control groups (transected rats). However, the addition of ascorbic acid or cholecalciferol to the basal diet increased the ADC and Fe retention in both transected and resected rats. Five weeks after surgery, resection also resulted in a reduced concentration of Fe in the sternum, but did not reduce the concentration of haemoglobin or serum Fe total Fe-binding capacity or the concentration of Fe in liver, testes, femur or muscle (longissimus dorsi). Supplementation with ascorbic acid increased serum Fe concentration, while the concentration of Fe in muscle was reduced by supplementation with both ascorbic acid and cholecalciferol. Neither supplementation had any effect on the Fe concentration in other tissues, on haemoglobin concentration or plasma total Fe-binding capacity. Thus, supplementation with ascorbic acid or with cholecalciferol increased Fe absorption and reduced the concentration of Fe in muscle.

Copper malabsorption after intestinal resection in rats. Effects of cholecalciferol and ascorbic acid.

Dietary modifications can partly compensate for the alterations in copper homeostasis caused by distal intestinal resection, by improving biliary function. We studied the effects of resecting 50% of the distal small intestine (DSI) on copper status in rats fed three semisynthetic diets (basal diet, and basal diet with cholecalciferol or ascorbic acid). Intestinal resection significantly decreased the digestive (apparent digestibility coefficient; ADC) and metabolic utilization (balance) of copper 1 month after surgery. However, the supplementation of the basal diet with cholecalciferol attenuated the negative impact of surgery, leading to small differences in Cu ADC and Cu balance between transected and resected rats. Ascorbic acid also enhanced copper retention. Copper status was not as markedly affected by intestinal resection as digestive utilization 1 month after the operation. The beneficial effects of cholecalciferol and ascorbic acid at the digestive and metabolic levels suggest ways to lessen the impact of intestinal resection, and to avoid possible long-term postabsorptive alterations in copper distribution.

Effect of intestinal resection, type of dietary fat and time on biliary lipid secretion in rats.

The effects of time and the type of dietary fat on biliary physiology in rats with 50% resection of the distal small intestine were investigated. The effects of ursodeoxycholic acid as an exogenous source of bile acid added to the diet were also studied. The fat composition of all diets was the same in quantitative terms (4%), and differed only in the type of lipid supplied: olive oil (diet A) or one-third medium chain triglycerides, one-third sunflower seed oil and one-third olive oil (diet B). In resected rats given diet A for 1 or 3 months, there was a decrease in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, with respect to the control group. Resected rats fed diet B for 1 or 3 months showed increases in biliary secretion of cholesterol and phospholipids, and in the lithogenic index, in comparison with resected rats fed diet A. The addition of ursodeoxycholic acid to diet B led to the decoupling of bile acid and bile lipid secretion.