High Iron Group Research Articles

Vertebral Bone Density Measurements by DXA are Influenced by Hepatic Iron Overload in Patients with Hemoglobinopathies

Interference from metal hardware (piercings; buttons on clothing; and ingested material, e.g. barium) is well documented in bone health assessments by dual-energy X-ray absorptiometry (DXA). It is unknown if iron in hepatic tissue of highly iron-loaded patients could be mistakenly assessed by DXA as bone, and if this would lead to increased areal bone mineral density (aBMD) lumbar spine Z-scores derived by DXA. Our hypothesis is that iron in the liver of heavily loaded patients will artificially raise aBMD in the spine, and thereby lead to an error in the DXA scan. This study consisted of a retrospective chart review and re-analysis of DXA scans from patients with sickle cell disease and thalassemia combined with prospective DXA and liver iron concentration (LIC) measurements from healthy controls. Patients who previously had both a DXA and LIC measurement were compared with controls. aBMD of individual vertebrae were analyzed and grouped by those that may be covered by the liver (L1 or L1/2) with those typically not (L3/4). Subjects were grouped by diagnosis and LIC severity. Phantoms were created to mimic the geometry of iron loaded liver tissue, and analyzed by DXA. A significant effect was observed in the difference of BMD Z-score of L1 and L 3/4 when patients with LIC < 1000 were compared to those with >5000 µg Fe/g wet tissue (p = 0.043). A significant relationship was also observed in the difference in aBMD Z-score of L1 and 3/4 when controls were compared to the high iron group (p = 0.037). These findings were supported by phantom experiments. These results suggest that there is a relationship between hepatic iron and increased L1 aBMD Z-scores in highly iron-loaded patients. Given patients with hemoglobinopathies are at increased risk for osteoporosis, clinicians should maintain a higher index of suspicion when diagnosing low bone mass.

Experimental study on the effect of hepcidin overexpression on osteoclasts and bone mass in iron accumulation mice

Objective: To investigate the effects of hepcidin on iron, osteoclasts and bone mass in iron accumulation mice. Methods: Eight-week old C57/BL6 male mice were divided into control group (CTR group), high iron group (Fe group) and iron reduction group (Hepc group). CTR group and Fe group were wild-type mice, Hepc group were hepcidin gene overexpression mice.Fe group and Hepc group were injected intraperitoneally with iron, and the mice in the CTR group were injected intraperitoneally with the same amount of saline.Three groups of mice were injected with tamoxifen to induce hepcidin overexpression.Eight weeks later, specimens of three groups of mice were collected and the serum levels of hepcidin, ferritin and carboxy-terminal telopeptides (CTX) were measured by enzyme linked immunosorbent assay (ELISA). Frozen section and Prussian blue stain were carried out to detect bone iron.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect osteoclast related gene expression[cytokinin (CTK), matrix metalloprotein (MMP9), protein tyrosine kinase 2β(PTK2β), cathepsin K (CTSK)]. Tartrate resistant acid phosphatase (TRAP) staining was used to observe the proliferation and differentiation of osteoclasts.The osteoclast activity was examined by lacunar resorption pits.The microstructure of the femur was measured by micro-computed tomography (Micro-CT). Variance analysis was applied to compare the differences among groups. Results: The levels of serum hepcidin in CTR, Fe and Hepc group were (508±42), (728±82) and (1 423±85) ng/L, respectively; serum ferritin were (355±26), (1 270±35) and (801±23) μg/L, respectively; CTX were (4.4±0.5), (13.9±1.4) and (8.5±0.6) mg/L, respectively; there were significant differences in the up-mentioned indexes among the three groups (F=129.6, 781.7, 77.3, all P<0.05). The genes expression level of CTK, MMP9, PTK2β, TRAP, CTSK in the Hepc and CTR group were all significantly lower than those in Fe group (F=39.6, 8.0, 5.4, 19.5, 8.8, all P<0.05). The results of TRAP staining and pits formation also showed that osteoclast proliferation and activity in group Hepc reduced significantly when compared with those in Fe group (t=4.295, 7.557, both P<0.05). Conclusion: The overexpression of hepcidin can down-regulate the content of ferritin in iron-accumulating mice and inhibit the proliferation, differentiation and activity of osteoclasts, and improve the bone mass.

Iron elevation and adipose tissue remodeling in the epididymal depot of a mouse model of polygenic obesity.

BackgroundIron dysregulation is a potential contributor to the pathology of obesity-related metabolic complications. KK/HIJ (KK) mice, a polygenic obese mouse model, have elevated serum iron levels. A subset of KK male mice display a bronzing of epididymal adipose tissue (eAT) associated with >100-fold (p<0.001) higher iron concentration.MethodsTo further phenotype and characterize the adipose tissue iron overload, 27 male KK mice were evaluated. 14 had bronzing eAT and 13 had normal appearing eAT. Fasting serum and tissues were collected for iron content, qPCR, histology and western blot.ResultsHigh iron levels were confirmed in bronzing eAT (High Iron group, HI) versus normal iron level (NI) in normal appearing eAT. Surprisingly, iron levels in subcutaneous and brown adipose depots were not different between the groups (p>0.05). The eAT histology revealed iron retention, macrophage clustering, tissue fibrosis, cell death as well as accumulation of HIF-2α in the high iron eAT. qPCR showed significantly decreased Lep (leptin) and AdipoQ (adiponectin), whereas Tnfα (tumor necrosis factor α), and Slc40a1 (ferroportin) were up-regulated in HI (p<0.05). Elevated HIF-2α, oxidative stress and local insulin signaling loss was also observed.SignificanceOur data suggest that deposition of iron in adipose tissue is limited to the epididymal depot in male KK mice. A robust adipose tissue remodeling is concomitant with the high iron concentration, which causes local adipose tissue insulin resistance.

Effect of Excess Iron Intake on Growth and Intestinal Inflammatory Injury in Rats

ObjectiveTo study the effects of excess iron intake on growth and development, and determine the possible mechanism.MethodsFourty eight male Wistar rats were randomly divided into 4 groups: low iron group, normal group, medium iron group, and high iron group, and received daily iron intake of 7mg/kg, 16.8mg/kg, 35mg/kg, and 70mg/kg in diet, and deionized water, respectively, for 8 weeks. The general condition, body weight, and food intake were documented during the study. Serum levels of Ferritin, IL‐6, IL‐10, and sIgA were measured using enzyme‐linked immunosorbent assay(ELISA).ResultsDuring the process of iron intervention, the high iron group had lower growth compared with the other three groups (p&lt;0.05). In addition, the levels of IL‐6 (108.60pg/ml) in small intestine were higher in the high iron group compared to the normal iron group (84.68pg/ml, P&lt;0.05), while serum levels of IL‐10 (50.47 pg/ml) in small intestine in the high iron group was lower than that in the normal iron group (71.69 pg/ml, (P&lt;0.05). Serum levels of sIgA (62.3pg/ml) in small intestine with the high iron group is lower than that in the normal iron group (67.1 pg/ml, P&lt;0.05). The histopathology showed normal morphology in the low iron and normal iron groups, however the rats in medium iron group showed slightly damaged mucosa, and lost apical microvilli. Irregular shape of microvilli and necrosis were found in a few epithelial cells of intestinal mucosa in the high iron group rats.ConclusionExcessive dietary iron intake has a negative affect on the normal growth and development of rats, and results in inflammatory injury in intestinal tract of rats.Support or Funding InformationThe National Natural Science Fund (No. 81373000)

Effects of Iron Overload on Growth and Intestinal Mucosa in Rats

Objective: To detect the mechanism of excess iron intake on growth and intestinal mucosa in rats. Methods: Forty-eight male Wistar rats were randomly divided into four groups: Low Iron Group, Normal Iron Group, Medium Iron Group and High Iron Group upon daily iron intake of 7mg/kg, 16.8mg/kg, 35mg/kg, 70mg/kg respectively via fodder for eight weeks. The general condition, body weight and food intake were documented simultaneously. Serum level of Ferritin, IL-6 and IL-10 were detected using ELISA. The observation of morphology of intestine was also included concurrently. Results: The weight obtained was significantly lower in the High Iron Group compared with the other three groups while the average weight of the rats in the High Iron Group was lower than the Normal Iron Group. Meanwhile, the average amount food uptake of the High Iron Group had slightly decreased in the eighth week. In addition, the level of IL-6 in small intestine of the High Iron Group is higher than that of the Normal Iron Group (P<0.05), while the level of IL-10 in small intestine of the High Iron Group is lower than that of the Normal Iron Group (P<0.05). The histopathology results showed that normal morphology was found in Low Iron Group and Normal Iron Group, but the mucosa showed a slight injury in the Medium Iron Group with apical microvilli slightly off. Irregular shape of microvilli and necrosis were found in some epithelial cells of intestinal mucosa in the High Iron Group. Conclusion: Excessive dietary iron intake plays a negative effect on the normal growth and development, and resulted in intestinal inflammatory injury in rats.

Iron Distribution in Dietary‐Induced Obese Mice Tissues

Iron homeostasis is required to maintain normal physiological processes such as oxygen delivery, DNA synthesis, and enzymatic reactions. An overall disturbance of iron homeostasis, e.g. systemic iron deficiency, was reported in obese subjects. The objective of this study was to examine tissue iron distribution in the dietary‐induced obese mice. Thirty male C57BL/6J mice were randomly assigned into six dietary treatment groups with various levels of iron (control, high and low) and fat (control and high) for 24 weeks. At the end of 24 weeks, tissues including liver, brain, heart, spleen and kidney were harvested and embedded in paraffin. Tissues were then processed and stained for iron using the Prussian blue reaction. Images were recorded using the Motic BA310 compound light microscope at 1000x magnification. Results showed that brain and spleen were the most responsive organs to dietary fat and iron treatments. In both brain and spleen, iron deposits were observed in high iron groups at both control and high fat levels. In the brain, iron deposits were surprisingly observed in mice treated with high fat low iron diet, indicating the vulnerability of brain to possible iron‐induced oxidative stress. To further evaluate overall brain iron disturbance by high fat diet, the expression of iron‐related proteins (storage, transport, and export proteins) and oxidative stress markers will be measured.

Iron deficiency in infancy: applying a physiologic framework for prediction

Infants aged 6-24 mo are at high risk of iron deficiency. Numerous studies worldwide have sought to identify predictors of iron deficiency in this age group. The objectives of the study were to apply a physiologic model to identify risk factors for iron deficiency and to consider those risk factors under different conditions of iron supplementation. We predicted that factors related to iron status at birth (lower gestational age and lower birth weight), postnatal needs for iron (more rapid growth), and bioavailable iron (more cow milk) would be major risk factors. The physiologic framework was assessed in 1657 Chilean infants (aged 12 mo) with birth weights >or=3 kg who were randomly assigned at age 6 mo to high or low iron supplementation or no added iron. Based on venous blood, the analysis used mean corpuscular volume and concentrations of hemoglobin, free erythrocyte protoporphyrin, and ferritin. Logistic regression models were used to identify predictors of iron deficiency anemia and iron deficiency without anemia. The prevalence of iron deficiency (>or=2 abnormal iron measures) was 34.9% at age 12 mo. Of 186 infants with hemoglobin concentrations <110 g/L, 158 (84.9%) were iron deficient. The only consistent (and the strongest) predictor of iron deficiency or iron deficiency anemia was lower 6-mo hemoglobin. Factors related to poorer iron status at birth (lower birth weight, shorter gestation though full-term, or both) were predictors in the no-added-iron and high-iron groups. Otherwise, predictors varied by iron supplementation. Variations in predictors of iron deficiency or iron deficiency anemia according to iron supplementation suggest that direct comparisons across studies are tenuous at best without data on early iron status and certainty that specific conditions are comparable.

The potentiating and protective effects of ascorbate on oxidative stress depend upon the concentration of dietary iron fed C3H mice

Ascorbic acid (AA) is an antioxidant that, in the presence of iron and hydrogen peroxide, increases the production of hydroxyl radicals in vitro. Whether AA has similar pro-oxidant properties in vivo may depend upon the relative balance of iron and AA concentrations. In this study, C3H mice were fed diets supplemented with 100 or 300 mg/kg iron, with or without AA (15 g/kg), for 12 months. Liver AA concentrations were greater in mice fed AA-supplemented diets with either low or high iron ( P=.0001), while the high-iron diet was associated with a significantly lower liver AA concentration regardless of AA supplementation ( P=.0001). Only mice fed the high-iron diet with AA had a significantly greater liver iron concentration ( P=.05). In the high-iron group, AA reduced oxidative stress, as measured by greater activities of glutathione peroxidase, superoxide dismutase (SOD) and catalase and by significantly lower concentrations of 4-hydroxylalkenal (HAE) and malondialdehyde (MDA). In mice fed the low-iron diet, AA was associated with greater concentrations of HAE and MDA and with lower activities of SOD. However, AA did not increase the concentrations of modified DNA bases with the low-iron diet but was associated with significantly lower concentrations of modified DNA bases in mice fed the high-iron diet. In conclusion, dietary AA appears to have mild pro-oxidant properties at low-iron concentrations but has a strong antioxidant effect against oxidative stress and DNA damage induced by dietary iron in mouse liver.

Increased Expression of Hypothalamic NADPH–Diaphorase Neurons in Mice with Iron Supplement

Iron deficiency is known as the most important nutritional problem in the world. The loss of appetite is a common characteristic of iron deficiency. Iron-containing heme is required as a cofactor for nitric oxide synthase (NOS) which produces nitric oxide (NO). NOS in the central nervous system has been suggested to regulate food intake. Hence, we examined the expression of hypothalamic NOS at various levels of dietary iron. ICR mice (n = 30) were randomly divided into three groups based on the level of dietary iron and fed experimental diets for 4 weeks: the normal-iron diet group (7 mg/kg diet, n = 10), the low-iron diet group (21 mg/kg diet, n = 10) and the high-iron diet group (42 mg/kg diet, n = 10). Expression of NOS in the paraventricular nucleus (PVN) and lateral hypothalamic area (LHA) of hypothalamus was examined by histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase). The high-iron diet mice showed significantly higher staining intensity of NADPH-diaphorase-positive neurons in the PVN and LHA than the normal- and low-iron diet mice.

Dietary Iron Affects Inflammatory Status in a Rat Model of Colitis

Iron deficiency anemia is a common feature in inflammatory bowel disease, and oral supplementation is one of the mainstay therapies. However, there is some concern that oral iron supplementation may lead to oxidative stress and exacerbation of inflammation. Our objective was to study the effect of severely deficient, moderately deficient, normal and high iron status on oxidative stress and the course of inflammation in a rat model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The rats were randomly assigned to receive the low-iron diet for 3 (moderately iron-deficient group, n = 16) or 5 (severely iron-deficient group, n = 16) wk, the normal iron diet for 2 wk (normal iron group, n = 16) or the high-iron diet for 2 wk (high-iron group, n = 16). Malondialdehyde concentration, electroparamagnetic resonance measurement, myeloperoxidase activity, and histological analysis were used to evaluate oxidative stress. Noncolitic rats in the high-iron group had higher oxidative stress parameters than those in the other groups. The induction of colitis resulted in severe inflammatory changes in the high-iron and severely iron-deficient groups, and produced higher histological scores in the colon of the normal and high-iron groups. Iron overload, oxidative stress, and inflammation were lower in the moderately iron-deficient group compared with the other 3 groups. In conclusion, we suggest that low rather than normal or high iron supplementation should be considered for the treatment of iron deficiency in inflammatory bowel disease.

A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants

Objectives: To investigate the effect of increased iron intakes on hematologic status and cognition in low birth weight infants. Study design: We randomly assigned 58 infants to receive formula with 13.4 mg iron/L (normal iron) or 20.7 mg iron/L (high iron). At baseline, discharge, and at 3, 6, 9, and 12 months’ corrected age, we assessed anthropometry; infections; red blood cell hemoglobin, catalase, glutathione peroxidase, red blood cell fragility (hydrogen peroxide test), and superoxide dismutase values; plasma malondialdehyde, ferritin, iron, transferrin, zinc and copper levels; and diet intake. Griffiths’ Development Assessment was done at 3, 6, 9, and 12 months only. Results: No statistical differences (P <.05) were noted for weight, catalase or malondialdehyde levels, red blood cell fragility, or Griffith’s Development Assessment. Iron intakes were greater in the high iron group except at 12 months. Hemoglobin (high iron, 123 ± 9; normal iron, 118 ± 8) was not different at 3 months (P =.07). Plasma zinc levels (high iron, 70 ± 14; normal iron, 89 ± 27) and copper levels (high iron, 115 ± 26; normal iron, 132 ± 27; P =.06) at 12 months suggested inhibition of absorption by high iron formula. Glutathione peroxidase levels were higher in the high iron group. The total number of respiratory tract infections was greater in the high iron group (3.3 ± 0.9) than in the normal iron group (2.5 ± 0.9). Conclusion: In terms of cognitive outcome, there is no advantage associated with elevated iron intake for low birth weight infants. (J Pediatr 2001;139:254-60)

Hepatic iron accumulation over time in European starlings (Sturnus vulgaris) fed two levels of iron.

European starlings (Sturnus vulgaris) were used as a passerine bird model to examine the effect of dietary iron on the level of hepatic iron in birds. Nestling and fledgling starlings (n = 56) were raised on a controlled-iron diet. When birds maintained constant body weight, they were assigned in pairs to cages, and baseline sampling was performed. Pairs were then assigned to one of two diets: the controlled-iron diet (168 ppm, dry basis) or a high-iron diet (3,035 ppm, dry basis). Dry-matter intake and iron consumption were recorded. Dry-matter intake did not differ between the dietary treatment groups and was stable during treatment periods. Iron intake was higher in the high-iron group (P < 0.05). Birds were euthanized at baseline, 8 wk, and 16 wk. Body, liver, and spleen weights were measured. Hepatic iron and copper concentrations were determined. Body weight did not differ between the two treatment groups or among individuals for the study duration. Liver iron concentration differed over time and between treatment groups. Birds receiving both treatments had similar liver iron content at week 8 (3,107 +/- 228.6 ppm and 3,122 +/- 306.2 ppm high and controlled iron, respectively; P > 0.05), but by week 16, birds consuming the high-iron diet had greater hepatic iron levels than those consuming the controlled-iron diet (5,929 +/- 937.2 ppm and 3,683 +/- 229.5 ppm high and controlled iron, respectively; P < 0.05). Birds on the controlled-iron diet also had higher hepatic iron at 16 wk than at 8 wk. Liver copper decreased over time in all birds regardless of treatment. Results show that both dietary iron level and duration of time influenced hepatic iron storage. The controlled-iron diets still allowed accumulation of hepatic iron in an 8-wk period.

Effect of Two levels of Iron Supplementation of Infant Formulas on Developmental Outcome and Iron nutrition in Very Low Birth Weight Infants† 1495

Conflicting opinions exist over the optimal amount of iron that low birth weight infants (LBW)should receive and for how long they should receive iron post discharge from hospital. Further,little information is available on the effect of poor iron nutrition on the neurodevelopmental outcome of LBW infants. We have previously demonstrated(CMAJ 1990:143;733-37)that 33% of LBW infants at 9 months of age fed an iron supplemented formula(12mg/l)for 6 months,had ferritin levels indicative of depleted iron stores. To investigate the effect of increased iron intakes on neurodevelopment, we randomly assigned infants at 2000g weight to receive either a formula with 12mg iron/l(iron) or 21 mg/l(high iron). The infants received either formula for a period of one year. At baseline, 3 months of age and 9 months of age the following measurements were taken: weight, hemoglobin, malondialdehyde (MDA), ferritin, and Griffiths Mental Develoment Scales. Statistical analysis between groups was with unpaired t-test using the Bonferonni correction for multiple comparisons. There were no statistical differences demonstrated between groups for any variables. There were no difference in birth weight or gestation between groups(bw=1432g ±390, gestation=31.5wks±2.3, N=29,iron group, N=31,high iron group). All statistics are reported as mean±sd. Table

Increases in the Concentrations of Available Iron in Response to Dietary Iron Supplementation Are Associated with Changes in Crypt Cell Proliferation in Rat Large Intestine , ,

High concentrations of iron in the diet have been shown to increase chemically induced colorectal tumors in rats. It is therefore important to understand the influence of dietary iron on the concentration of unabsorbed iron in the large intestine and its distribution between soluble and insoluble pools in the luminal compartment. We sought to investigate this issue and to establish whether iron modifies mucosal cell proliferation, which is thought to influence initiation and progression through the adenoma carcinoma sequence. In the first experiment, four groups of seven rats were fed diets at two concentrations of iron, 29 and 102 mg/kg, with or without the addition of 2.5 g phytic acid/kg. The concentrations of iron in the contents of the large bowel extractable with water (“free iron”) or a buffered EDTA solution (“exchangeable iron”) were determined. The concentration of freely soluble iron increased ∼100% with iron supplementation in both the cecum and the colon, and there was an approximately five- to sixfold increase in exchangeable iron at both sites (P < 0.05). In a second experiment with identical feeding conditions, there was a significantly greater number of cell divisions per crypt in the colon of the high iron group and a significantly greater number of cell divisions in the upper part of the crypt in the cecum. The concentrations of free and exchangeable iron observed in colonic contents in this study are consistent with those reported by others to increase free radical production in fecal material. Further studies are required to determine whether the small changes in crypt cytokinetics are a consequence of oxidative mucosal damage.

Role of low molecular weight iron in functional preconditioning of the isolated rat heart.

Post-ischemic contractile dysfunction in the heart may be due to oxygen-derived free radicals catalyzed by low molecular weight iron (lmw Fe), which is thought to accumulate during ischemia and reperfusion. We tested the hypothesis that functional preconditioning with transient ischemia in the rat heart may be due to decreasing the myocardial lmw Fe pool, and consequently free radicals during ischemia or reperfusion. Hearts were preconditioned with two 5-min episodes of ischemia followed by 5 min of reperfusion. The lmw Fe pool of pre-ischemic hearts was 172 +/- 13pmol/mg protein. After 40 min of prolonged ischemia, the lmw Fe contents were 176 +/- 25 and 127 +/- 13 pmol/mg for non-conditioned and preconditioned hearts, respectively (P=N.S.). After 10 min of reperfusion, the lmw Fe contents were 246 +/- 26 and 228 +/- 23 pmol/mg protein, respectively (P=N.S.). We next tested the ability of deferoxamine, an iron chelator, to mimic functional preconditioning. The percentage recoveries of heart rate x developed pressure after 40 min of ischemia and 30 min of reperfusion were 38 +/- 6 and 25 +/- 5 for non-conditioned and deferoxamine-treated hearts, respectively (P=N.S.). We further tested the hypothesis by determining if iron-overloading by dietary enhancement and weekly iron injections would exacerbate post-ischemic contractile dysfunction and attenuate functional preconditioning with ischemia. The total iron contents of the high iron and normal groups were 10.3 +/- 0.6 and 4.4 +/- 0.2 nmol/mg protein (P<0.001). Percentage recoveries of heart rate x developed pressure were 36 +/- 6 and 33 +/- 5 for non-conditioned hearts in the high iron and normal iron groups, respectively (P=N.S.). Percentage recoveries of heart rate x developed pressure were 58 +/- 5 and 68 +/- 6 for ischemically preconditioned hearts in the high and normal iron groups, respectively (P= N.S.). The results suggest that functional preconditioning in the rat heart is not due to attenuation lmw Fe accumulation.

Effects of alpha-tocopherol and beta-carotene on hepatic lipid peroxidation and blood lipids in rats with dietary iron overload.

The ability of dietary antioxidants to reduce lipid peroxidation induced by iron overload was examined in weanling male Sprague-Dawley rats. Animals were fed ad libitum a modified AIN-76A diet (control) or control diet with 0.5% alpha-tocopherol acid succinate, 0.5% crystalline trans-beta-carotene, or 0.5% alpha-tocopherol acid succinate + 0.5% trans-beta-carotene for four weeks. In the following four-week period, the animals received the above diets with 10,000 micrograms Fe/g; a control group continued to receive 35 micrograms Fe/g, and a high-iron group received 10,000 micrograms Fe/g with no antioxidants. After four weeks of dietary supplementation with alpha-tocopherol. Beta-carotene or alpha-tocopherol + beta-carotene, liver concentrations of alpha-tocopherol and beta-carotene increased significantly (p < 0.001). Liver lipid peroxidation, measured by the lipid-conjugated diene assay, increased significantly from 0.012 mumol/mg of lipid in the controls to 0.021 mumol/mg of lipid in animals receiving the high-iron diet. However, lipid peroxidation was significantly reduced in all animals fed the antioxidants, with the group fed alpha-tocopherol + beta-carotene having a lower level than the high-iron group. Total serum cholesterol was elevated in animals fed a high-iron diet and in animals fed the high-iron diet with alpha-tocopherol. In contrast, total serum cholesterol levels in the two groups of animals receiving the diets containing high iron with beta-carotene alone or high iron with beta-carotene + alpha-tocopherol were significantly reduced to the level of the control group. High-density lipoprotein cholesterol also decreased to baseline in the animals receiving beta-carotene alone. Modulation of lipid peroxidation by alpha-tocopherol or beta-carotene may be an important mechanism for reducing oxidative stress.

Effects of Dietary Iron Concentrations on the Cytochrome P450 System of Atlantic Salmon (Salmo salar)

Groups of Atlantic salmon (Salmo salar) parr were fed a basal diet containing 27 mg Fe∙kg feed−1 supplemented with different iron levels (0, 80, and 160 mg∙kg−1, respectively) for 8 wk. After this period, a subgroup of each iron regime was treated intraperitoneally with β-naphthoflavone (BNF), a potent inducer of cytochrome P450 1A1 in fish. Differences between the iron regimes were observed in hepatic iron content, which was higher in the high-iron group, and in P450 1A1 levels and monooxygenase activity, measured as 7-ethoxyresorufin O-deethylase (EROD), which were lower in the high-iron group. Differences were also observed in the induction response of P450 1A1 and EROD to BNF. Levels of a constitutive isozyme denoted P450con, belonging to the P450 3A subfamily, did not respond to the dietary iron in the same manner, demonstrating selective regulatory effects of iron on different P450 isozymes.

Evaluation of Two Iron-Fortified, Milk-Based Formulas During Infancy

Compare milk-based, iron-fortified formulas containing 7.4 and 12.7 mg/L iron and breast-feeding during the first year of life. Partially randomized, double-blind trial: non-breast-fed infants randomly assigned to receive one of two coded formulas, identical except for iron content; infants discontinuing breast-feeding between 1 and 8 weeks of age randomly assigned to a formula late-start group. Five general community pediatric practices in Missouri, Indiana, Illinois, and Pennsylvania. Sample of 347 healthy, term infants, enrolled within 1 week after birth; 172 included in statistical analyses. Length, weight, and indicators of formula intolerance recorded at clinic visits; formula consumption, bowel movements, stool consistency, and other tolerance indicators recorded by parents on daily and weekly report forms; hemoglobin, hematocrit, and serum ferritin, iron zinc, and copper measured at 6 and 12 months. No significant differences between formula-fed groups in growth, attrition, formula consumption, bowel movements, hematocrit, hemoglobin level, and serum iron, zinc, and copper levels (P > .05); first 6-month weight and length changes of the breast-fed group significantly less than in both formula-fed groups (P < .008); serum ferritin level of the formula-fed, high-iron group significantly higher than that of the low-iron and breast-fed groups (P < .008), although all groups' values were normal; no apparent differences between formula groups in formula tolerance and stool characteristics but data were not analyzed statistically. Milk-based formulas containing either 7.4 or 12.7 mg/L iron support normal growth and iron status of healthy, term, normally fed infants during the first year and both are well tolerated and accepted.

Macrophage Function as Studied by the Clearance of 125I-Labeled Polyvinylpyrrolidone in Iron-Deficient and Iron-Replete Mice

This study evaluated the effects of iron deficiency and iron repletion on in vivo macrophage function determined by the clearance of 125I-labeled polyvinylpyrrolidone (PVP). Two experiments were done. There were four groups of C57BL/6 female mice in experiment 1: the iron-deficient (ID), pair-fed (PF), control (C) and the high iron (HI) groups. In experiment 2, there were three ID groups (severe to moderate anemia), three PF, one C and four ID groups that were fed adequate iron for 14 (R-14), 7 (R-7), 3 (R-3) days before or on the day of PVP injection (R-0). The overall rate of PVP clearance from blood was lower in ID than in C or PF groups. This clearance is expressed by a constant, K, calculated from natural log (ln) of the cpm and the time postadministration of PVP that blood was drawn. The theoretical individual macrophages function (αPVP), derived from K and the weights of body, spleen and liver, was also lower in ID than in C or PF groups. The impairment was most severe with the most severe iron deficiency. Repletion for 7 to 15 d before PVP administration resulted in a partial correction of the clearance. Moderate undernutrition in the PF group had no effect.

The chemistry and origin of the ordinary chondrites: Implications from refractory‐lithophile and siderophile elements

Thirty‐eight ordinary chondrites (17 H, 20 L, and 1 LL) have been analyzed for major and selected trace elements. These data indicate that the lithophile elements Mg, Ca, Al, Cr, and V normalized to Si are in higher abundance in the H than in the L chondrites. The siderophile elements Ni, Co, and Fe show very good correlation within, as well as between, the two major ordinary chondrite groups. Twenty‐four of our analyses are of Antarctic finds, while ten are samples of falls. Comparing the Antarctic data with the fall data reveals no evidence that any of the elements studied here have been mobilized by terrestrial weathering processes. Within the H and L chondrite groups there is little chemical variation, indicating that the source of these samples is remarkably homogeneous. Equilibrium condensate fractionation from a nebula of CI composition can result in the observed ordinary chondrite compositions. The fractionation of metal at about 1440°K (and 10−3 atm) into high and low iron groups, followed by a gas‐solid fractionation at about 1380°K with the H group losing more solids than the L, will produce the observed H and L compositions and intragroup trends.