Iron supplementation improves endurance after training in iron-depleted, nonanemic women.

Our objective was to investigate the effects of iron depletion on adaptation to aerobic exercise, assessed by time to complete a 15-km cycle ergometer test. Forty-two iron-depleted (serum ferritin <16 microg/l), nonanemic (Hb >12 g/dl) women (18-33 yr old) received 100 mg of ferrous sulfate (S) or placebo (P) per day for 6 wk in a randomized, double-blind trial. Subjects trained for 30 min/day, 5 days/wk at 75-85% of maximum heart rate for the final 4 wk of the study. There were no group differences in baseline iron status or in 15-km time. Iron supplementation increased serum ferritin and decreased transferrin receptors in the S compared with the P group. The S and P groups decreased 15-km time and respiratory exchange ratio and increased work rate during the 15-km time trial after training. The decrease in 15-km time was greater in the S than in the P group (P = 0.04) and could be partially attributed to increases in serum ferritin and Hb. These results indicate that iron deficiency without anemia impairs favorable adaptation to aerobic exercise.     

Metabolic capacity regulates iron homeostasis in endothelial cells

The sensitivity of endothelial cells to oxidative stress and the high concentrations of iron in mitochondria led us to test the hypotheses that (1) changes in respiratory capacity alter iron homeostasis, and (2) lack of aerobic metabolism decreases labile iron stores and attenuates oxidative stress. Two respiration-deficient (rho(o)) endothelial cell lines with selective deletion of mitochondrial DNA (mtDNA) were created by exposing a parent endothelial cell line (EA) to ethidium bromide. Surviving cells were cloned and mtDNA-deficient cell lines were demonstrated to have diminished oxygen consumption. Total cellular and mitochondrial iron levels were measured, and iron uptake and compartmentalization were measured by inductively coupled plasma atomic emission spectroscopy. Iron transport and storage protein expression were analyzed by real-time polymerase chain reaction and Western blot or ELISA, and total and mitochondrial reactive oxygen species (ROS) generation was measured. Mitochondrial iron content was the same in all three cell lines, but both rho(o) lines had lower iron uptake and total cellular iron. Protein and mRNA expressions of major cytosolic iron transport constituents were down-regulated in rho(o) cells, including transferrin receptor, divalent metal transporter-1 (-IRE isoform), and ferritin. The mitochondrial iron-handling protein, frataxin, was also decreased in respiration-deficient cells. The rho(o) cell lines generated less mitochondrial ROS but released more extracellular H(2)O(2), and demonstrated significantly lower levels of lipid aldehyde formation than control cells. In summary, rho(o) cells with a minimal aerobic capacity had decreased iron uptake and storage. This work demonstrates that mitochondria regulate iron homeostasis in endothelial cells.     

Iron stores in female blood donors evaluated by serum ferritin

Iron stores were evaluated by serum ferritin determinations in 948 menstruating and 141 non-menstruating female blood donors. Blood donation was associated with a decrease in ferritin. First-time donors (n = 163) had a geometric mean ferritin of 24 micrograms/l and multiple-time donors a value of 19 micrograms/l (p less than 0.01). In the donating population 31.5% had ferritin values less than 15 micrograms/l (i.e. depleted iron stores). Menstruating donors had lower mean serum ferritin than non-menstruating donors (p less than 0.001), and a higher frequency of ferritin values less than 15 micrograms/l (p less than 0.05). There was no relationship between ferritin levels and the number of pregnancies. The frequency of donations was more predictive of ferritin levels than the number of donations. Mean ferritin displayed a moderate fall up to the 2nd donation, and was hereafter relatively constant, whereas an increase in donation frequency was accompanied by a significant decrease in ferritin. Female donors, especially when phlebotomised greater than or equal to 3 times per year, should have their iron status checked at appropriate intervals by measurement of serum ferritin and should be advised regular iron supplementation.     

Daily supplementation with iron increases lipid peroxidation in young women with low iron stores

The aim of this study was to determine whether women with low iron stores (plasma ferritin 相似文献   

Effects of iron deficiency on the secretion of interleukin-10 by mitogen-activated and non-activated murine spleen cells

Interleukin (IL)-10 plays crucial regulatory roles in immune responses by inhibiting the secretion of several cytokines (IL-2, IL-12, interferon-gamma (IFN-gamma)) and lymphocyte proliferation. Iron deficiency, a public health problem for children, alters these immune responses. To determine whether these changes are related to altered IL-10 secretion, we measured IL-10 in 24 and 48 h supernatant of spleen cell cultures from iron deficient (ID), control (C), pairfed (PF), and ID mice fed the control diet (iron repletion) for 3 (R3) and 14 (R14) days (d, n = 12/group). Mean levels of hemoglobin, hematocrit, and liver iron stores varied as follows: C approximately equal PF approximately equal R14 > R3 > ID (P < 0.01). Mean baseline IL-10 levels of ID mice tended to be higher than those of other groups (P > 0.05, ANOVA). Mean IL-10 levels secreted by concanavalin A (Con A) and antibody raised against cluster of differentiation molecule 3 (anti-CD3)-treated cells (+/-background) were lower in ID than in C (48 h) and iron replete mice (P < 0.05). Underfeeding also reduced IL-10 secretion by anti-CD3-treated cells (48 h, P < 0.05). Lymphocyte proliferative responses to anti-CD3 +/- anti-CD28 antibodies were lower in ID than in C and PF mice, and they were corrected by iron repletion (P < 0.05). IL-10 levels negatively correlated with indicators of iron status (r 相似文献   

Iron depletion without anemia is not associated with impaired selenium status in college-aged women

Iron-deficiency anemia has been shown to alter body mineral concentrations and activities of iron- and non-iron-containing enzymes, especially those with antioxidant functions. These effects, however, have been less studied in nonanemic iron-depleted individuals. Thus, this study assessed indices of selenium status in 12 college-aged females with adequate iron stores and 15 college-aged females with low iron stores before and after iron therapy. Blood samples were drawn at baseline for both groups and following iron supplementation in the low-iron-stores group. Hematocrit, hemoglobin, and serum ferritin concentrations of the low-iron-stores group were significantly lower than those of the control group. The serum transferrin receptor-to-serum ferritin ratio in the low-iron-stores group was significantly greater than that of the control group. Serum selenium and glutathione peroxidase concentrations of the low-iron-stores group were not significantly different from those of the controls. Iron supplementation significantly increased hemoglobin, hematocrit, and serum ferritin concentrations and significantly decreased the serum transferrin receptor concentration and serum transferrin receptor:serum ferritin ratio in the low-iron-stores group posttreatment compared to pretreatment. Serum selenium and glutathione peroxidase concentrations did not differ significantly from pretreatment to posttreatment in the low-iron-stores group. Results of this study indicate that low iron stores without anemia are not associated with impaired selenium status in college-aged females.     

Differential effects of iron deficiency and underfeeding on serum levels of interleukin-10, interleukin-12p40, and interferon-gamma in mice

BACKGROUND: Over-production of interferon-gamma (IFN-gamma) and under-production of interleukin-10 (IL-10) are associated with autoimmunity, whereas the opposite is associated with overwhelming infections. The influence of iron deficiency, a public health problem for children on in vivo secretion of these cytokines has not been previously investigated. OBJECTIVE: To determine whether iron deficiency alters serum levels of IFN-gamma, IL-10, and IL-12 in mice. DESIGN AND METHODS: Cytokine levels were measured by enzyme immunoassay in iron-deficient (ID), control (C), pair-fed (PF), and iron replete C57BL/6 mice for 3 (R3) and 14 (R14) days (n = 24-28, 12 R14). RESULTS: Iron deficiency was associated with > or = 50% reduction in hemoglobin, hematocrit, liver iron stores, and thymus weight (p < 0.05). Iron repletion improved these measurements. While iron deficiency significantly reduced IL-12p40 (64%) and IFN-gamma (66%) levels, underfeeding reduced those of IL-10 (48%) (p < 0.05). Iron repletion improved cytokine concentrations to PF levels. Thymus atrophy observed in 16 ID and 19 R3 mice, had no effect on IL-12p40 and IFN-gamma, whereas it further decreased IL-10 levels by 72% (p < 0.05). Cytokine levels positively correlated with indicators of iron status, body and thymus weights (r < or = 0.688, p < 0.05). CONCLUSION: Data suggest that iron deficiency alters the balance between pro- and anti-inflammatory cytokines, a change that may affect innate and cell-mediated immunity, and risk of autoimmune disorders.     

Iron stores in Chinese eligible male plateletpheresis donors

Plateletpheresis donors may become iron deficient, particularly if donating at the maximum suggested interval of every 2 weeks. This study aimed to evaluate iron stores in male Chinese plateletpheresis donors. Serum samples were collected from 445 male plateletpheresis donors and serum ferritin (SF) levels were measured. There were 16 repeat donors (3.6%) with iron deficiency (SF<10 ng/mL), but none was found in first time donors. About 63 (14.2%) had depleted iron stores (SF<30 ng/mL), including two first time donors (0.4%). Repeat donors had lower mean SF levels than the first donors. There was a positive correlation between iron deficiency/depletion prevalence, lower hemoglobin level and number of platelet donations. Donation interval, age and ABO blood groups were not associated with iron status. Iron status needs to be monitored in repeat platepheresis donors and donors with Hb<130 g/L, especially when the number of donations are between 10 and 30. For these individuals, SF measurement and iron supplementation are recommended.     

Iron and transferrin uptake by phytohemagglutinin-stimulated human peripheral blood lymphocytes

Iron (Fe) and transferrin (TF) uptake by human peripheral blood lymphocytes stimulated in vitro with phytohemagglutinin was measured. Pulses of 59FeTF or 125I-TF were added to the cultures either at time 0 or 8 hr before the end of a 72-hr incubation. In time-course experiments, peak iron and transferrin uptake coincided with the peak of tritiated thymidine uptake taken as a measure of cellular activation. Iron, but not transferrin, was accumulated by the cells. Non-linear relationships existed between both iron and transferrin uptake and the degree of activation. Both rose markedly above basal levels only at a level of activation at least 50% of the maximum observed. The results suggest that although iron utilization is related to cellular activity, the uptake mechanism is only activated when an increased iron metabolism has exhausted internal stores.     

Iron metabolism is modified by the copper status of a human erythroleukemic (K562) cell line.

Copper deficiency is known to result in a microcytic, hypochromic anemia. Red cells of copper-deficient animals have less hemoglobin than their copper-adequate counterparts. The objective of this work was to determine what role copper plays in maintaining hemoglobin levels. It was hypothesized that the primary defect lies in intracellular iron metabolism. The influence of copper supplementation on iron uptake and storage was examined in a cell line capable of hemoglobin synthesis. The results demonstrated that copper supplementation of human K562 cells was associated with higher cytosolic iron levels and ferritin levels. Copper supplementation of the cell culture altered the initial rate of iron uptake from transferrin and enhanced iron uptake in noninduced cells; however, in hemin-induced K562 cells, which express fewer transferrin receptors on the cell surface, copper appeared to reduce iron uptake. Subsequent studies showed that the cells were able to take up the same amount of iron from transferrin when incubated over a longer period of time (24 hr). In the noninduced (non-hemoglobin synthesizing) cells, proportionally more iron was associated with the ferritin. We concluded from these studies that copper affects both uptake and storage of iron and that copper supplementation reduces cellular iron turnover.     

Iron metabolism of established human hematopoietic cell lines in vitro

Three malignant hematopoietic cell lines were used in studies on cellular iron metabolism. Our results show that iron-carrying transferrin became bound to specific dimeric cell surface receptors. Iron accumulated within the cell with time, whereas intact transferrin was released back to the medium. Chloroquine and NH₄Cl, known as pH-raising agents in vesicles of the lysosomal system, inhibited iron accumulation and transferrin binding in a dose-dependent manner. This suggests that the acid pH in endosomes leads to the cleavage of the iron-transferrin bonds. Transferrin degradation was not found, which leads us to suggest a process of ‘acid flushing’ for the dissociation of iron from transferrin without the involvement of endosome-lysosome fusion. Taken together, the data agree with the concept of receptor-mediated endocytosis, as described for many macromolecules. Iron was stored in ferritin in the cell types tested. Only a minor part (less than 15%) of the iron was bound in hemoglobin in the K-562 cell line. The relationship between iron stores and exogenously added iron in heme synthesis was investigated using a double labelling (⁵⁵Fe/⁵⁹Fe) technique. The results showed that exogenous iron was preferentially used before the iron stored in ferritin. The results are discussed in relation to various hypotheses on cellular iron uptake and transport.     

Differential expression of iron metabolism proteins in diabetic and diabetic iron-supplemented rat liver

Diabetes mellitus is associated with altered iron homeostasis that can potentially effect reactive oxygen species generation and contribute to diabetes-related complications. We investigated, by quantitative polymerase chain reaction, whether the expression of liver hepcidin, ferritin, and TfR-1 is altered in diabetes. Rats in the control (C) group received a standard diet; control iron (CI) group received a standard diet supplemented with iron; diabetic (D) group received an injection of streptozotocin; and diabetic iron (DI) group received streptozotocin and the diet with iron. Animals of the D group showed higher levels of serum iron, increased concentration of carbonyl protein, and a decrease in antioxidant status. Group D rats showed increased hepatic expression of Trf-1 compared to the other groups. Iron supplementation reversed this increase. Hepcidin mRNA was 81% higher in DI than in C and CI rats. The results suggest that diabetes, with or without excess iron, can cause perturbations in iron status, hepcidin and Trf-1 expression.     

Can iron be teratogenic?

Several kinds of evidence indicate that elevated iron during the 3–8 week embryonic (organogenesis) period of human gestation may be teratogenic. (1) In the embryonic period, the natural maternal absorption of food iron is 30% below the estimated daily iron loss. (2) As compared with maternal serum, embryonic fetal coelomic fluid contains only one-fourth as much iron but nearly six times the quantity of the iron withholding protein, ferritin. (3) In the embryonic period, intraplacental oxygen pressure is 2–3 times lower than in the subsequent fetal growth period. (4) Iron is a strong inducer of emesis which peaks in the embryonic period. (5) In a murine gestation model, iron was neurotoxic at a sharp peak of 8–9 days. Thus it would be prudent, in human pregnancy, to delay any needed iron supplementation until the embryonic period has been completed.     

Effect of an iron supplement on body iron status and aerobic capacity of young training women

Serum iron deficiency has a high incidence in female athletes. We investigated the effects of a daily oral iron supplement, (160 mg) administered during an intensive 7-week physical training programme, on body iron status, and the maximal aerobic capacity (VO2max) of 13 women (group A) compared to 15 who took a placebo (group B). The subjects were 19 years old. Blood samples were obtained before training began and on days 1, 7, 21 and 42 of training. They were analysed for packed cell volume (PVC) and for haemoglobin (Hb), 2,3-diphosphoglycerate (2,3-DPG), haptoglobin, iron and ferritin concentrations. The VO2max was measured on days 0, 21 and 42 of training. Following 21 days of training Hb, PCV and ferritin were significantly higher (P less than or equal to 0.01) in group A compared to group B. Over the training period Hb rose by 9.3% and 2.4% in groups A and B, respectively. At the end of training 66% of group B exhibited ferritin concentrations below 10 ng.ml-1, while none of group A had such low values. Mean VO2max of group A had increased by 7.5% following 21 days of training (P less than or equal to 0.01) and by 15.3% after 42 days. No appreciable increase in VO2max had occurred in group B by day 21 (significantly lower than VO2max of group A; P less than or equal to 0.05), however by day 42 it had increased by 14.3% (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of iron and/or vitamin A re-supplementation on vitamin A and iron status of rats after a dietary deficiency of both components

Iron and vitamin A deficiency are common nutritional problems in developing countries. From animal experiments and intervention studies, growing evidence is pointing to a possible influence of iron on vitamin A metabolism. We assessed the affects of an oral supplementation of vitamin A and/or iron on the recovery of rats from vitamin A and iron deficiency. Weanling male Wistar rats were kept for four weeks on an iron and vitamin A deficient diet. Thereafter, rats were repleted with iron 35 mg/kg feed, with vitamin A 4500 IU/kg feed both, or with iron 35 mg/kg and vitamin A 4500 IU/kg for five weeks. Retinol and retinyl esters in plasma and tissues were determined by HPLC. Iron was determined by atomic absorption spectrophotometry. The determination of haematological parameters showed that rats developed an anaemia during depletion. This was reversed by the re-supplementation with iron but not vitamin A alone. The simultaneous supplementation of vitamin A was of no additional benefit. When rats were resupplemented with iron alone a substantial further decrease in plasma retinol (P < 0.002) and liver vitamin A (P < 0.05) was observed. A similar but less pronounced decrease in plasma retinol was observed in the rats re-supplemented with vitamin A alone, despite a substantial increase in liver vitamin A (P < 0.002). Despite lower liver vitamin A levels compared to the group re-supplemented with vitamin A lone, the group re-supplemented with iron and vitamin A had substantial higher plasma levels compared to the one supplemented with iron alone (P < 0.002). In conclusion, the study supports an interaction of iron and vitamin A on the level of retinol transport in plasma. Despite a comparable availability of vitamin A as indicated by the comparable liver levels only the re-supplementation of both iron and vitamin A can normalize the retinol level in plasma. This might be of nutritional consequence in developing countries with regard to the supplementation regime of both nutrients iron and vitamin A to prevent a functional deficiency of vitamin A despite sufficient dietary availability.     

Response of blood serum constituents to production of and recovery from a kwashiorkor-like syndrome in the young pig.

Twenty-six 3-week-old genetically obese pigs were fed in two experiments to determine the serum chemistry profile during severe protein malnutrition and repletion. Severe protein deficiency was produced in pigs fed the high-fat, low-protein diet (growth failure, rough hair, low serum total protein and albumin). In Experiment 1, blood was sampled from the anterior vena cava of each pig five times during depletion and three times during repletion to determine serum total cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, total protein, albumin, glucose, Ca, inorganic P, Mg, Na, K, Cl, total bilirubin, urea N, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase. In Experiment 2, blood was sampled weekly for 8 weeks for serum total cholesterol, HDL-cholesterol, triglycerides, albumin, glucose, Ca, P, Mg and alkaline phosphatase. HDL-cholesterol was increased (P less than 0.01) and albumin was decreased (P less than 0.01) in protein-deficient pigs in both experiments. Creatinine, total bilirubin, gamma-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase were elevated in protein-deficient pigs compared with controls after 7 weeks of depletion. Inorganic P (P less than 0.01), Ca (P less than 0.01), and Mg (P less than 0.05) concentrations were depressed in protein-depleted pigs compared with controls in both experiments. After 8 weeks of repletion in Experiment 1, all elements except inorganic P were similar in the two groups. Short-term, severe, protein malnutrition affected lipid, electrolyte, and structural mineral metabolism and indices of liver function in the absence of parasites, diarrhea, and infection. The effects were reversed after 8 weeks of repletion. We conclude that the elevated serum cholesterol in protein deficiency is related primarily to an increase in the HDL fraction.     

Kinetics of tissue RRR-alpha-tocopherol depletion and repletion. Effect of cold exposure

Vitamin E was estimated in plasma and tissues of rats kept for three months on a low vitamin E diet or a high vitamin E diet. Some of the animals from each group were switched to the opposite diet, and the kinetics of uptake and depletion of vitamin E were followed 3, 8, and 15 days after the diet change. Some rats were also submitted to cold exposure (6 degrees C) for three days. During repletion plasma, red blood cells, liver, spleen, and adrenal gland were the only tissues that responded rapidly to the diet change; after three days, their vitamin E levels corresponded to that of the new diet. Heart, brain, lung, muscle, and thymus were slow in reacting to diet change. Fifteen days after the change in diet, white adipose tissue did not respond. The rate of repletion for all tissues was more rapid than the rate of depletion, but liver was the only tissue that after three days had vitamin E levels corresponding to the low-vitamin diet. Cold exposure for three days did not produce any significant change in the vitamin E content of any tissue, indicating that despite high oxygen consumption by the animal, vitamin E was not consumed or mobilized.     

Ethanol-induced iron mobilization: role of acetaldehyde-aldehyde oxidase generated superoxide

Superoxide radicals, a species known to mobilize ferritin iron, and their interaction with catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury. The mechanism(s) by which ethanol metabolism generates free radicals and mobilizes catalytic iron, however, is not fully defined. In this investigation the role of hepatic aldehyde oxidase in the mobilization of catalytic iron from ferritin was studied in vitro. Iron mobilization due to the metabolism of ethanol to acetaldehyde by alcohol dehydrogenase was increased 100% by the addition of aldehyde oxidase. Iron release was favored by low pH and low oxygen concentration. Mobilization of iron due to acetaldehyde metabolism by aldehyde oxidase was completely inhibited by superoxide dismutase but not by catalase suggesting that superoxide radicals mediate mobilization. Acetaldehyde-aldehyde oxidase mediated reduction of ferritin iron was facilitated by incubation with menadione, an electron acceptor for aldehyde oxidase. Mobilization of ferritin iron due to the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism of alcohol-induced liver injury.