Rat Ferritin Research Articles

Erythropoietin hyporesponsiveness in non-alcoholic fatty liver disease.

Treatment with erythropoietin (EPO) can correct anaemia in chronic kidney disease (CKD) patients; however, up to 10% exhibit resistance or hyporesponsiveness to EPO. Non-alcoholic fatty liver disease (NAFLD), prevalent liver disease in CKD patients, may limit EPO response because of thrombopoietin deficiency, iron homeostasis disorder and inflammation. Therefore, we hypothesized NAFLD is a risk factor for EPO responsiveness. To test our hypothesis, we evaluated the effect of EPO in healthy rats and rats with NAFLD induced by a high-fat, high-carbohydrate (HFHC) diet. After 12 weeks on the HFHC diet, NAFLD rats showed lower erythroid response to EPO treatment than healthy rats. We, then, determined that the primary cause of EPO hyporesponsiveness could be iron deficiency associated with inflammation, which reduces erythroid cell production. Specifically, the concentrations of hepcidin, ferritin, transferrin and white blood cells in NAFLD rats were 12.8-, 16.4-, 2.51- and 1.40-fold higher than those in healthy rats, respectively. However, erythroid cell types in the bone marrow of NAFLD rats were significantly reduced. In conclusion, our data suggest that NAFLD could be a risk factor for EPO responsiveness, which is attributed to functional iron deficiency associated with inflammation.

Enhanced Expression of Hepatic Genes in Copper-Deficient Rats Detected by the Messenger RNA Differential Display Method

The influence of copper (Cu) status on hepatic gene expression was examined by using the “messenger RNA differential display” technology. This method involves the distribution of mRNA in a two-dimensional array for the rapid identification and cloning of differentially expressed genes. Livers from male Sprague-Dawley rats that had been fed a Cu-deficient (CD) diet (9.4 µmol/kg) or a Cu-adequate (CA) diet (103.9 µmol/kg) for 6 wk were used to supply cytosolic RNA. Cytosolic RNA were reverse-transcribed in the presence of anchor primers and then amplified by polymerase chain reaction with anchor and arbitrary primer sets. The amplified cDNA were then resolved by denaturing polyacrylamide gel electrophoresis. Differences in mRNA expression between the CD and CA rats were identified. DNA fragments were cloned, sequenced and used as probes for Northern blot analysis to confirm that the identified genes were differentially expressed. The analysis of cDNA sequences by computer searches against DNA and protein databases revealed that one cDNA fragment, whose mRNA abundance was enhanced 1.2-fold by copper deficiency, is novel. Four other cDNA fragments were found to have substantial homology with rat ferritin mRNA; rat fetuin mRNA; rat mitochondrial 12S and 16S rRNA, phenylalanine-, valine- and leucine-tRNA genes; rat mitochondrial genes for 16S rRNA, tRNA-leucine and tRNA-valine; and their mRNA abundance was 0.6- to 0.8-fold higher in Cu-deficient rats. Five additional cDNAs detected by this method appeared to represent novel genes because they exhibited no substantial homology to recorded gene and protein sequences deposited in DNA and protein data-bases. These results demonstrate the usefulness of this technology in the detection of genes which were differentially expressed as a result of the deprivation of a single nutrient, dietary copper, in this research project.

Electroacupuncture Reduces Cerebral Hemorrhage Injury in Rats by Improving Cerebral Iron Metabolism.

Objective To study the effects of electroacupuncture at Baihui and Dazhui points on the expression of hepcidin (Hepc), transferrin (Tf), transferrin receptor (TfR), and ferritin (Ft) in rats with cerebral hemorrhage to provide a theoretical basis for the treatment of cerebral hemorrhage with acupuncture. Method The model of cerebral hemorrhage in rats was established by autologous blood injection method and treated by electroacupuncture (EA) at the acupoints of Baihui and Dazhui. Hepc siRNA was injected into the lateral ventricle 30 min before model preparation to produce the cerebral hemorrhage model. The modified neurological severity score (mNSS) was used to assess the neurological function, and the total iron content in brain tissue was determined using atomic absorption spectrometry; the expression of Hepc, Ft, Tf, and TfR in perihematoma tissue was detected using immunohistochemistry; the interference efficiency of Hepc siRNA was detected using western blot and reverse transcription polymerase chain reaction (RT-PCR). Results The degree of neurological deficit showed a downward trend at 3 days, 7 days, and 14 days, and electroacupuncture significantly reduced the neurological deficit score at each time point (P < 0.01). Regarding total iron content in brain tissue, on the 3rd day, the 7th day, and the 14th day, the iron content of the hematoma tissue after intracerebral hemorrhage was reduced by electroacupuncture (P < 0.01). Regarding immunohistochemical results. Hepc, Ft, Tf, and TfR protein expressions on day 14 were significantly higher after cerebral hemorrhage (P < 0.01). After electroacupuncture, the expression of Hepc, Ft, Tf, and TfR protein was significantly reduced (P < 0.01). Western blot and RT-PCR revealed that the interference efficiency of Hepc siRNA was statistically significant (P < 0.01). Conclusion Electroacupuncture can reduce neurological severity scores in rats with cerebral hemorrhage and may exert cerebral protective effects by reducing Hepc protein and gene expression; lowering Ft, Tf, and TfR protein expression; and promoting iron metabolism in the brain of rats with cerebral hemorrhage.

Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats

ABSTRACT Objective Iron deficiency and vitamin A deficiency are two of the main micronutrient deficiencies. Both micronutrients are essential for human life and children's development. This study aimed to investigate the effects of vitamin A deficiency on ferritin and transferrin receptors' expression and its relationship with iron deficiency. Methods Five diets with different vitamin A-to-iron ratios were given to thirty five 21-day-old male Wistar rats (separated in groups of seven animals each). The animals received the diet for six weeks before being euthanized. Serum iron and retinol levels were measured as biochemical parameters. Their duodenums, spleens, and livers were analyzed for the expression of ferritin and transferrin receptors by Western Blotting. Results Regarding biochemical parameters, the results show that when both vitamin A and iron are insufficient, the serum iron content (74.74µg/dL) is significantly lower than the control group (255.86µg/dL). The results also show that vitamin A deficiency does not influence the expression of the transferrin receptor, but only of the ferritin one. Conclusion Vitamin A deficiency regulates the expression of ferritin in young male Wistar rats.

Vitamin A does not influence mRNA expression of hormone hepcidin but other biomarkers of iron homeostasis in young male Wistar rats.

The effects of an adequate supply of vitamin A and iron, in comparison with diets low or absent in vitamin A and low in iron, on the mRNA expression of some biomarkers of iron homeostasis as hepcidin (Hamp), transferrin receptor-1 (Tfrc), iron regulatory protein-2 (Ireb2) and ferritin (Fth1) in rats were investigated. 35 male Wistar rats were randomly divided into 5 dietary groups: control, sufficient in iron and insufficient in vitamin A (FesvAi), sufficient in iron and depleted in vitamin A (FesvAd), insufficient in iron and sufficient in vitamin A (FeivAs) and insufficient in both iron and vitamin A (FeivAi). After 6 weeks rats showed no significant effects of variations in vitamin A on the expression of Hamp relative to the control group (FesvAi: 1.37-fold; FesvAd: 1.22-fold); however, iron deficiency showed significant reduction on it relative to the control group (FeivAs: 71.4-fold, P=0.0004; FeivAi: 16.1-fold, P=0.0008). Vitamin A deficiency (FesvAd) affects expression of Fth1 independent of low dietary iron in spleen (0.29-fold, P=0.002) and duodenum (5.15-fold, P=0.02). Variations of dietary iron and vitamin A showed significant effects relative to the control group for expression of Tfrc in spleen (FesvAd: 0.18-fold, P=0.01; FeivAs: 0.24-fold, P<0.0001; FeivAi: 0.42-fold, P=0.014), Ireb2 in spleen (FeivAs: 3.7-fold, P<0.0001; FeivAi: 2.9-fold, P<0.0001) and Ireb2 in duodenum (FeivAs: 2.68-fold, P=0.012; FeivAi: 2.60-fold, P=0.014). These results show that vitamin A and iron must be supplied together to regulate some of the main biomarkers of iron metabolism as a strategy to reduce prevalence of iron deficiency anemia.

Verapamil reverses cardiac iron overload in streptozocin-induced diabetic rats

Accumulating evidence shows that iron overload is a new risk factor for diabetes mellitus. L-type Ca(2+) channel (LTCC) has been identified as an important mediator for ferrous iron uptake into cardiomyocytes. In this study, we aimed to examine the effects of verapamil, the LTCC blocker, on myocardial iron metabolism in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozocin after intragastric administration of fat emulsion, and then treated by verapamil (5 mg · kg(-1) · day(-1)) for 1 week. The results showed that verapamil did not alter the blood glucose level of diabetic rats. However, elevated levels of superoxide dismutase, malonaldehyde, and serum ferritin in diabetic rats were decreased significantly by verapamil treatment. Moreover, serum, myocardial, and urine iron were elevated remarkably along with a decrease of hepatic iron in diabetic rats. After verapamil administration, serum and myocardial iron in diabetic rats were reduced significantly but urine and hepatic iron were increased. Furthermore, confocal microscopy demonstrated that intracellular-free iron concentration was elevated dramatically in cardiomyocytes of diabetic rats, which was markedly attenuated after verapamil treatment. In summary, our data demonstrated that verapamil prevented myocardial iron overload by inhibiting intracellular iron accumulation in diabetic cardiomyocytes.

Glial cell activity is maintained during prolonged inflammatory challenge in rats

We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

Proanthocyanidins Inhibit Iron Absorption from Soybean (Glycine max) Seed Ferritin in Rats with Iron Deficiency Anemia

The objective of this study was to evaluate the effect of proanthocyanidins (PAs) on iron uptake from soybean seed ferritin (SSF) crude by rats with iron deficiency anemia (IDA) for the first time. Six groups of Sprague-Dawley (SD) rats (n = 10) were used, which contain (1) SSF crude group; (2) SSF crude + PAs group; (3) PAs group; (4) FeSO(4) group; (5) iron deficiency control group; and (6) control group. The bioavailability of iron was examined by measuring hemoglobin (Hb) concentration value, red blood cell (RBC) numbers, and serum iron stores. After 8 weeks, Hb concentration was almost recovered to the normal level upon feeding SSF crude or FeSO(4) to rats. In contrast, Hb concentration was recovered to less extent when SSF crude plus PAs was used instead of SSF crude alone (P < 0.05). A similar profile was observed with these three sample groups when serum iron and RBC were used as parameters. All rats in PAs group died at the 8th week. Taken together, all these results demonstrated that PAs inhibited iron uptake of rats from SSF, and are toxic for rats with IDA.

Rapid Regulation of Intestinal Divalent Metal (Cation) Transporter 1 (DMT1/DCT1) and Ferritin mRNA Expression in Response to Excess Iron Loading in Iron-Deficient Rats

We determined the effects of excess iron on the expression of duodenal divalent metal transporter 1 (DMT1) and ferritin (Ft) in iron-deficient rats which had increased iron absorption. DMT1 mRNA was down-regulated and Ft mRNA was up-regulated 2 h after administering the iron. However, more than 2 h was needed for Ft protein synthesis to occur in the duodenal mucosa.

MRI of the basement membrane using charged nanoparticles as contrast agents

The integrity of the basement membrane is essential for tissue cellular growth and is often altered in disease. In this work a method for noninvasively detecting the structural integrity of the basement membrane, based on the delivery of cationic iron-oxide nanoparticles, was developed. Cationic particles accumulate due to the highly negative charge of proteoglycans in the basement membrane. The kidney was used to test this technique because of its highly fenestrated endothelia and well-established disease models to manipulate the basement membrane charge barrier. After systemic injection of cationic or native ferritin (CF or NF) in rats, ex vivo and in vivo MRI showed selective accumulation of CF, but not NF, causing a 60% reduction in signal intensity in cortex at the location of individual glomeruli. Immunofluorescence and electron microscopy demonstrated that this CF accumulation was localized to the glomerular basement membrane (GBM). In a model of GBM breakdown during focal and segmental glomerulosclerosis, MRI showed reduced single glomerular accumulation of CF, but a diffuse accumulation of CF in the kidney tubules caused by leakage of CF through the glomerulus. Cationic contrast agents can be used to target the basement membrane and detect the breakdown of the basement membrane in disease.

Hepato and nephroprotective activities of Ruta graveolens and Sophora japonica and their flavonoids in normal and carcinogenic rat model

The present study was carried out to investigate the anti-carcinogenic effect of Ruta graveolens and Sophora japonica and their flavonoids (rutin and quercetin) in both normal and carcinogenic rats. A total umber of 238 albino rats were used. The animals were divided into 2 major groups each of 119 rats (normal and carcinogenic group induced by DMBA and TPA). Each group was subdivided into 17 groups, each composed by 7 rats, and each group orally received daily either 10% or 20% of LD50 of n-hexane (0.45, 1.28g/Kg,) or ethyl acetate (2.64, 3.10g/Kg) or chloroform extract (0.21, 0.89g/Kg) of Ruta graveolens or Sophora japonica plants or its flavonoids either rutin or quercetin. So, 10% and 20% administration of the LD50 of each of medicinal plant or their flavonoids were responsible for significant and highly significant decrease in serum glucose level. Moreover, significant decrease in serum cholesterol, low density lipoprotein and triglycerides while significant increase in blood superoxide dismutase and glutathione peroxidase were detected in the treated groups. Serum selenium and zinc were also increased after treatment with 20% of the LD50 of either flavonoids or flavonoid-containing medicinal plant extracts. Flavonoids and flavonoid-containing medicinal plants had no effect on liver and kidney functions as well as tumor markers (serum alpha-fetoprotein and ferritin) in normal rats. Administrating of both flavonoids and flavonoid-containing medicinal plant extracts to carcinogenic rats restored serum glucose, liver and kidney functions, lipid fractions, tumor markers and antioxidants to approach the normal level. Conclusion: The studied flavonoids and flavonoids-containing medicinal plant extracts had hypoglycemic, hypocholesterolemic, anticarcinogenic as well as antioxidant activity.

High level expression of proteins using sequences from the ferritin heavy chain gene locus

An expression vector has been generated using a gene highly expressed under conditions found in a typical fed-batch bioreactor process. The ferritin heavy chain (HC) gene exhibits higher levels of expression in the late stages of a fed-batch bioreactor than in the early stages. This property was considered advantageous for an expression vector, since the maximal cell density would coincide with maximal expression. The rat ferritin HC genomic region was isolated and converted into an expression vector where large segments of 5' and 3' flanking regions were included in an attempt to recreate the same high level of expression in stably transfected cells. Expression from the resulting ferritin HC vector was compared to vectors containing the commonly used strong promoters, CMV IE, and SV40 early promoter/enhancer, in the generation of stable transfectants. The ferritin HC vector was able to generate cell lines with significantly higher expression levels than those under the control of the viral promoters.

Identification of a 250 kDa putative microtubule‐associated protein as bovine ferritin

We reported previously on the purification and partial characterization of a putative microtubule-associated protein (MAP) from bovine adrenal cortex with an approximate molecular mass of 250 kDa. The protein was expressed ubiquitously in mammalian tissues, and bound to microtubules in vitro and in vivo, but failed to promote tubulin polymerization into microtubules. In the present study, partial amino acid sequencing revealed that the protein shares an identical primary structure with the widely distributed iron storage protein, ferritin. We also found that the putative MAP and ferritin are indistinguishable from each other by electrophoretic mobility, immunological properties and morphological appearance. Moreover, the putative MAP conserves the iron storage and incorporation properties of ferritin, confirming that the two are structurally and functionally the same protein. This fact led us to investigate the interaction of ferritin with microtubules by direct electron microscopic observations. Ferritin was bound to microtubules either singly or in the form of large intermolecular aggregates. We suggest that the formation of intermolecular aggregates contributes to the intracellular stability of ferritin. The interactions between ferritin and microtubules observed in this study, in conjunction with the previous report that the administration of microtubule depolymerizing drugs increases the serum release of ferritin in rats [Ramm GA, Powell LW & Halliday JW (1996) J Gastroenterol Hepatol11, 1072-1078], support the probable role of microtubules in regulating the intracellular concentration and release of ferritin under different physiological circumstances.

Inhibition of Nicotine-Induced Toxicity by Curcumin and Curcumin Analog: A Comparative Study

The present study was undertaken to evaluate the effects of curcumin and curcumin analog on blood oxidant-antioxidant status during nicotine-induced toxicity in male Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks). The enhanced circulatory lipid peroxides in nicotine-treated rats was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase. There was a reduction in the levels of zinc with an elevation of copper and ferritin in nicotine-treated rats. Administration of curcumin and curcumin analog significantly lowered the lipid peroxidation and enhanced the antioxidant status with modulation in the levels of zinc, copper, and ferritin. However, the effect was more significant in curcumin analog-treated rats than in curcumin-treated rats. The results of the present study suggest that curcumin and curcumin analog exert their protective effects by modulating the extent of lipid peroxidation and enhancing the antioxidant status.

Dietary Iron Status Has Little Effect on Expression of Ceruloplasmin but Alters That of Ferritin in Rats

Evidence supports a role for ceruloplasmin (ferroxidase I) in the release of iron to the blood from mammalian cells. However, recent studies with cultured cells have suggested that it has the opposite effect, and that iron deficiency enhances expression of ceruloplasmin. We therefore examined in rats how nutritional iron status would affect expression of ceruloplasmin. Groups of male Sprague-Dawley rats were reared on a low iron, starch-based diet for 6-8 wk; half were supplemented by injection of iron dextran. At killing, hematocrits of deficient rats were half normal. Supplemented rats had normal liver concentrations of ferritin and ferritin iron. No ferritin was detected in the livers of the deficient rats. Northern analysis showed that ferritin L and H mRNAs were present in the deficient livers, but expression was half that of the normal rats. There was also twice as much copper. Levels of circulating ceruloplasmin (measured by rocket immunoelectrophoresis) were not altered by iron deficiency, although p-phenylenediamine oxidase activity and plasma copper were reduced approximately 30%. In repeated studies, no differences in the expression of hepatic ceruloplasmin mRNA were detected. Treatment of rats of both sexes with additional iron (25 mg as iron dextran) 5-14 d before killing increased liver ferritin but did not alter liver ceruloplasmin mRNA expression or levels of circulating ceruloplasmin. We conclude that iron status is not an important factor in the expression of plasma ceruloplasmin made by the liver. However, it does have modest effects on steady-state levels of liver ferritin mRNA.

Purification and Properties of a Folate-catabolizing Enzyme

We have identified and purified to homogeneity an enzyme from rat liver that catalyzes the oxidative catabolism of 5-formyltetrahydrofolate to p-aminobenzoylglutamate and a pterin derivative. Purification of the enzyme utilized six column matrices, including a pterin-6-carboxylic acid affinity column. Treatment of crude rat liver extracts with EDTA or heat decreased the specific activity of the enzyme by up to 85%. Peptides generated from the purified protein were sequenced and found to be identical to primary sequences present within rat light chain or heavy chain ferritin. Commercial rat ferritin did not display catabolic activity, but activity could be acquired with iron loading. The purified enzyme contained 2000 atoms of iron/ferritin 24-mer and displayed similar electrophoretic properties as commercial rat liver ferritin. The ferritin-catalyzed reaction displayed burst kinetics, and the enzyme catalyzed only a single turnover in vitro. Expression of rat heavy chain ferritin cDNA resulted in increased rates of folate turnover in cultured Chinese hamster ovary cells and human mammary carcinoma cells and reduced intracellular folate concentrations in Chinese hamster ovary cells. These results indicate that ferritin catalyzes folate turnover in vitro and in vivo and may be an important factor in regulating intracellular folate concentrations.

Structure and location of a ferritin gene of the yellow fever mosquito Aedes aegypti.

We have isolated and sequenced a genomic clone encoding the 24- and 26-kDa ferritin subunits in the mosquito Aedes aegypti (Rockefeller strain). The A. aegypti gene differs from other known ferritin genes in that it possesses an additional intron and an unusually large second intron. The additional intron is located within the 5' untranslated region, between the CAP site and the start codon. The second intron contains numerous putative transposable elements. In addition, unlike the human and rat ferritin genes, the A. aegypti ferritin gene is a single copy gene, located at 88.3% FLpter on the q-arm of chromosome 1. Primer extension analysis indicates that the A. aegypti ferritin gene has multiple transcriptional start sites. A differential usage of these sites is observed with varied cellular iron concentrations.

Identification of regulated genes in rat heart after myocardial infarction by means of differential mRNA display.

In order to testify the hypothesis that unknown mechanisms are involved in the process of cardiac remodeling after myocardial infarction (MI), we employed differential display reverse transcription-polymerase chain reaction (DDRT-PCR) as our primary inspection tool. An animal model of MI was established by ligation of the left anterior descending coronary artery (LAD) in rat. Fifty upregulated candidate cDNA fragments were obtained in the right ventricle (RV) of the heart six weeks after MI. Eight cDNA fragments isolated from DD denaturing gel were extracted and reamplified, cloned into pCR II vector and sequenced. A Genbank search of these clones showed that three of them have a high homology with known genes not previously associated with cardiac remodeling, i.e., mouse interleukin-4 receptor gene, rat ferritin mRNA, and T-cell receptor beta chain V beta 5. The remaining clones have no similarity to known sequences. These data suggest that certain genes which were not previously being associated with cardiac hypertrophy are turned on during the process of cardiac remodeling after MI.

Iron and Phosphate Content of Rat Ferritin Heteropolymers

An attempt was made to relate the iron and phosphate content of ferritin to its subunit composition. Ferritins from various tissues were separated according to their subunit composition by anion exchange chromatography and according to their iron content by density-gradient centrifugation. Iron and phosphate contents were not related to subunit composition. Recombinant rat liver ferritin heteropolymers of different subunit composition (1, 4, 6, 10, 15, and 17 H chains per 24 mer) were maximally loaded with iron, using ceruloplasmin and phosphate. All loaded approximately the same amount of iron and phosphate (2250 and 380 atoms, respectively). The iron and phosphate content of all ferritin, including the maximally loaded recombinant ferritin heteropolymers, fit an equation we previously reported: [Fe] = 4404 − 5.61 [Pi] (D. deSilvaet al.,1993,Arch. Biochem. Biophys.303, 451–455). These results suggest that the amount of iron and apparently the space within the core of ferritin were not related to different subunit composition.

Influence of iron supplementation frequency on absorption efficiency and mucosal ferritin in anaemic rats.

It is believed that frequent Fe doses decrease the efficiency of absorption as a consequence of the loading of intestinal mucosal cells with Fe from the previous supplemental dose. We examined this premise in thirty anaemic Sprague-Dawley rats given Fe supplements as FeSO4 in 1 g preparations of a 50:50 (w/w mixture of low-Fe diet and sucrose under one of the following regimens: one 3 mg Fe dose daily for 3d, four 0.75 mg doses daily at 6 h intervals for 3 d, and one 9 mg dose on day 1 followed by two placebo (low-Fe diet) doses on days 2 and 3. All groups were fed on two low-Fe meals daily (8.3 mg Fe/kg diet). After an overnight fast rats were dosed with 1 ml of an 59Fe-labelled ferric nitrilotriacetic acid solution (37 kBq 59Fe, 50 micrograms Fe) orally and killed 10 h later. Absorption of 59Fe was measured as the percentage of the 59Fe retained by the carcass without the gastrointestinal tract 10 h after dosing relative to the initial 59Fe dose. Haemoglobin-Fe gain, liver non-haem-Fe, and mucosal duodenal ferritin were determined after the 3 d supplementation period. Absorption of the test dose in rats supplemented once 3 d before assessment of Fe absorption was 2.6-fold greater than those supplemented with daily single doses and 1.9-fold greater than those supplemented with daily multiple doses. Our data indicate that both mucosal ferritin and liver Fe levels account for the higher absorption efficiency found in rats supplemented once to simulate intermittent regimens.