Zinc, cadmium, and iron interactions during intestinal absorption in iron-deficient mice

1978 ◽  
Vol 56 (3) ◽  
pp. 384-389 ◽  
Author(s):  
D. L. Hamilton ◽  
J. E. C. Bellamy ◽  
J. D. Valberg ◽  
L. S. Valberg

Zinc absorption from a test dose of (65Zn) zinc chloride was increased in mice with a high capacity to absorb iron induced by a low-iron diet. When radiolabelled zinc chloride in concentrations varying from 0.025 to 0.30 mM was perfused through open-ended duodenal loops of mice fed this diet, the proportion of zinc taken up from the lumen and transferred to the body was greater from lower than from higher doses. The addition of iron to the perfusate inhibited zinc uptake and transfer, and zinc had a similar effect on iron absorption. Cadmium, a potent inhibitor of iron uptake in mice fed a low-iron diet, impaired zinc uptake under these dietary conditions. These results suggest that in dietary-induced iron deficiency there are analogous mucosal binding sites for the uptake of iron and zinc. There also appear to be mutually exclusive binding sites for the absorption of these metals: radiolabeled iron absorption from an intragastric test dose was enhanced in mice with a high capacity to absorb iron produced by bleeding, whereas the absorption of zinc was not increased.

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1885 ◽  
Author(s):  
Palsa Kondaiah ◽  
Puneeta Singh Yaduvanshi ◽  
Paul A Sharp ◽  
Raghu Pullakhandam

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation and food fortification. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly, increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating intestinal iron absorption and mobilization from tissues. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN1) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN1 axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.


2018 ◽  
Vol 11 (3) ◽  
pp. 85 ◽  
Author(s):  
Eka Ginanjar ◽  
Lilik Indrawati ◽  
Iswari Setianingsih ◽  
Djumhana Atmakusumah ◽  
Alida Harahap ◽  
...  

Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO4 or NaFe(III)EDTA with water, revealed that FeSO4 was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency. All subjects received a placebo, 6.5 mg FeSO4, 65 mg FeSO4, 6.5 mg NaFeEDTA, and 65 mg NaFeEDTA with a traditional Indonesian breakfast in one-week intervals. Blood tests were carried out every 60 min for five hours. NTBI detection was performed using the fluorescein-labeled apotransferrin method. Plasma iron values were highly increased after 65 mg NaFeEDTA, twice as high as after FeSO4. A similar pattern was seen for NTBI. After 6.5 mg of NaFeEDTA and FeSO4, NTBI was hardly detectable. NaFeEDTA was highly effective for the treatment of iron deficiency if given with a meal, inhibiting the formation of nonabsorbable Fe-complexes, while NTBI did not exceed the range of normal values for iron-replete subjects.


1964 ◽  
Vol 207 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Georg W. Strohmeyer ◽  
Stephen A. Miller ◽  
Robert W. Scarlata ◽  
Edward W. Moore ◽  
Mortimer S. Greenberg ◽  
...  

Rats exposed to an atmosphere of 10% oxygen increase their absorption of a test dose of iron after 6 8 hr. Release of tissue storage iron begins within 2 hr of the start of hypoxia and continues for at least 8 hr. An oral iron load does not prevent the release of tissue iron in response to hypoxia. Iron-loaded rats also release iron from storage depots and increase their minimal absorption in response to hypoxia. Iron-deficient rats apparently have a diminished tissue release and also increase absorption above their elevated base-line levels. Xanthine loading had no effect on the release of tissue iron or changes in absorption with hypoxia, and there was no evidence that changes in xanthine oxidase activity in the liver or bowel were directly associated with tissue release or absorption of iron.


Blood ◽  
1973 ◽  
Vol 42 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Yvan C. Bédard ◽  
Peter H. Pinkerton ◽  
Géerard T. Simon

Abstract The uptake of iron by the absorptive cells of the duodenum, and its subsequent transfer to the lamina propria, has been studied using 55Fe and high-resolution radioautography in mice rendered iron deficient by diet, in mice with dietary iron overload, and in mice with hereditary malabsorption of iron (s/a). In all, as in normally iron replete mice, two phases of iron absorption can be distinguished. There is an early active phase of uptake and transfer, followed by a second "storage" phase. The pathway of iron absorption is qualitatively similar to the normal with rapid uptake by the brush border, passage through the terminal web to the rough endoplasmic reticulum, and areas rich in free ribosomes. Iron passes through the lateral cell membrane, intercellular spaces and epithelial basement membrane to the vessels of the lamina propria. The rough endoplasmic reiculum and areas rich in free ribosomes form the major localization of iron at all stages of absorption. Only a relatively small amount of radioactive iron is found over ferritin in iron-loaded mice and mice with s/a; morphologically recognizable ferritin was not observed at any stage in iron-deficient animals. Significant numbers of grains have not been seen over mitochondria in any group of animals studied. In iron-deficient mice, the rate of uptake and of transfer of iron is increased. With the 10 µg dose of iron used, all iron taken up by the absorptive cell is transferred to the lamina propria within 3 hr, with none remaining in the cell during the second, storage phase. In mice with iron overload, transfer of iron is decreased, resulting in considerable storage of iron in the cell. In s/a mice, uptake does not appear to be unduly reduced, but transfer is reduced, thereby resulting in increased storage of iron in the absorptive cell. The rough endoplasmic reticulum and areas rich in free ribosomes appear to play an important role in the uptake, transfer, and storage of iron by the absorptive cell regardless of the state of the body iron stores. Ferritin would seem to have a less important part in iron absorption, possibly acting as a storage or detoxifying mechanism.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2338-2338
Author(s):  
Annelies J. Van Vuren ◽  
Joannes J.M. Marx ◽  
Richard van Wijk ◽  
Eduard J. van Beers

Abstract Introduction Patients with hereditary hemochromatosis (HH) and non-transfusion-dependent hereditary anemia (HA NTD) both express low hepcidin levels, leading to increased intestinal iron absorption and, ultimately, predominantly parenchymal iron overload. Knowledge about iron absorption in humans stems from iron absorption or utilization studies with radio-labeled iron performed in the 60-70s from the last century. Here, we present unique data of combined absorption and utilization studies in a large cohort of patients with primary and secondary hemochromatosis. Methods We retrospectively analyzed the data from iron absorption and kinetics studies performed from 1972 until 1994 as part of routine clinical practice in patients with iron-related health problems at the University Medical Center Utrecht, the Netherlands. A radioactive tracer dose of oral (1 mg) 59Fe with 51Cr as non-absorbable indicator, or intravenous (10 µCi) 59Fe was administered. Radio-activity was measured with a whole-body counter to assess absorption and with a gamma-counter to determine radio-activity in peripheral blood samples to calculate the amount of iron utilized for red blood cell (RBC) production. Main findings Iron absorption was analyzed in 6 distinct groups with and without iron overload and iron reducing therapy (table). Iron uptake is the percentage of the iron test dose taken up by enterocytes, retention the percentage retained in the body 14 days after ingestion, and transfer the fraction of iron taken up that is retained in the body. Iron uptake, transfer and retention were significantly higher in patients with treated and untreated HH and iron deficiency (ID) compared with healthy controls (p<0.01). Notably, uptake, transfer and retention were also significantly higher in the analyses of patients with treated or untreated HA NTD (including 19 congenital sideroblastic anemia, 6 hereditary spherocytosis, 5 congenital dyserythropoietic anemia, 3 non-transfusion dependent thalassemia, 4 Hb Adana, 2 hexokinase deficiency and 1 PKD) than in analyses of healthy controls (p<0.01). Next, iron retention was used to calculate the percentage of iron utilized for RBC production after 14 days. Mean percentages of RBC iron utilization (RBCIU) after an oral iron test dose were 37% (SD 17%) in untreated HA NTD, 53% (SD 19%) in treated HA NTD, 55% (SD 20%) in untreated HH, 70% (SD 22%) in treated HH, and 99% (SD 22%) in ID patients. Surprisingly, RBCIU was lower after oral than after intravenous iron in patients with HA NTD or HH (figure 1). The difference between oral and intravenous RBCIU was expressed as percentage of intravenous RBCIU, and denominated as the LIR (liver iron retention). The LIR had a mean value of 28% (SD 26%) in untreated HH, 23% (SD 24%) in untreated HA NTD, and 16% (SD 25%) in treated HH patients, all significantly higher than the LIR of 1% (SD 22%) measured in ID patients (p<0.05). The LIR was strongly correlated to iron saturation (r=0.41; p<0.01). Main conclusions Of major interest is the observation that a substantial fraction of oral iron retained in patients with iron overload was not utilized for erythropoiesis. Under circumstances of high transferrin saturation, a part of iron transported from enterocytes into the portal circulation will be non-transferrin-bound iron (NTBI). A part of this NTBI will be available as labile plasma iron (LPI), a form of iron with high redox potential, and the capacity to rapidly cross membranes via transporters and channels. Recently it was shown that in iron-overloaded conditions LPI is almost completely taken up after passage of the liver and this is facilitated by ZIP14 in a non-transferrin-dependent way. (Jenkitkasemwong et al. Cell Metabolism, 2015: 22(1), 138-150). We therefore hypothesize that LPI produced primarily in the portal system (oral dosed iron) is primarily taken up in the liver and that LPI produced elsewhere in the circulation (intravenous dosed iron) may be taken up by other organs as well. In conclusion, our data is suggestive of the existence of significant hepatic scavenging of NTBI/LPI under iron-overloaded conditions. This could explain the distinct patterns of transfusion-dependent and transfusion-independent iron overload and we suggest that ZIP14 could facilitate this. Disclosures van Wijk: Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; RR Mechatronics: Research Funding. van Beers:RR Mechatronics: Research Funding; Bayer: Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.


1987 ◽  
Vol 58 (03) ◽  
pp. 936-942 ◽  
Author(s):  
Lindsey A Miles ◽  
Edward F Plow

SummaryGlu-plasminogen binds to platelets; the monocytoid line, U937, and the human fetal fibroblast line, GM1380 bind both plasminogen and its activator, urokinase. This study assesses the interaction of these fibrinolytic proteins with circulating human blood cells. Plasminogen bound minimally to red cells but bound saturably and reversibly to monocytes, granulocytes and lymphocytes with apparent Kd values of 0.9-1.4 μM. The interactions were of high capacity with 1.6 to 49 × 105 sites/cell and involved the lysine binding sites of plasminogen. Both T cells and non-rosetting lymphocytes and two B cell lines saturably bound plasminogen. Urokinase bound saturably to gianulocytes, monocytes, non-rosetting lymphocytes and a B cell line, but minimally to T cells, platelets and red cells. Therefore, plasminogen binding sites of high capacity, of similar affinities, and with common recognition specificities are expressed by many peripheral blood cells. Urokinase receptors are also widely distributed, but less so than plasminogen binding sites. The binding ol plasminogen and/ or urokinase to these cells may lead to generation of cell- associated proteolytic activity which contributes to a variety of cellular functions.


1984 ◽  
Vol 51 (03) ◽  
pp. 349-353 ◽  
Author(s):  
C Caranobe ◽  
P Sié ◽  
F Fernandez ◽  
J Pris ◽  
S Moatti ◽  
...  

SummaryA simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient’s platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient’s platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.


Author(s):  
R. Stavetska ◽  
Y. Dynko ◽  
M. Bushtruk ◽  
I. Starostenko ◽  
O. Babenko ◽  
...  

It has been experimentally proven that the strength and direction of the connection between the linear type traits evaluation of the Ukrainian black-and-white dairy breed cows and their body build depends on the type of the build and the sign of the exterior. The study was conducted in 2018 on a breeding plant of the Ukrainian Black-and-White Dairy breed SPC named Shchorsa in Kiev region (n=89). Differentiation of cows on types of their body build was conducted by the method proposed by Chernenko (low-capacity, mid-capacity and high-capacity types) and Kolesnik (by the massiveness index – on the friable and dense, the bone index – delicate and rough, the wide-breast and wide-rump indices – on narrow-body and wide-body types). It was found that the cow-heiferswere well-developed, had intermediate stature and optimum body condition score, deep body, and wide, slight slope rump. They alsohad desirable rear legs, set and foot angle but some toe-out, the udder was well-balanced. Under the good total score of the exterior of studied cows there were some animals with short stature (134– 136 cm), very wide rump, straight rear legs side view and toe-out, extremely steep foot angle, loose fore udder attachment, deep udder below hocks and front teat placement inside of quarter. The degree of development of the studied linear traits of cow-heifers confirms their in-herd variability. The variability of the exterior traits varies from 10,7 % (body depth) to 38,6 % (stature). In addition to the stature of a significant variability was characterized of angularity (22,4 %), rear legs set (22,5 %), body condition score (21,8 %), as well as traits that describe udder: rear udder attachment (31,4 %), udder depth (32,6 %) and front and rear teat position (31,3 % and 25,1 %, respectively). The high variability of linear traits indicates the possibility of effective their selection. As a result of the research, it has been established that the strength and direction of the correlations between the linear type traits evaluation of Ukrainian Black-and-White Dairy breed cows and the type of their body build depends on the type of the body build and the linear trait. The low-, mid- and high-capacity bodies build types (according to Chernenko) reliably correlate with chest width (r=0,58) and body depth (r=0,48), rear legs rear view (r=0,30), the central ligament (r=0,28), udder depth (r =-0,22) and teat length (r=0,25), P˂0,01–0,001. Friable and dense bodies build (according to Kolesnik) were most strongly associated with stature (r=-0,28), chest width (r =-0,70), and body depth (r=-0,38), as well as with rear legs rear view (r=-0,23), P˂0,05...0,001; delicate and rough bodies build – with stature (r=-0,51), angularity (r=-0,22),rump width (r=-0,35), udder depth (r=-0,27) and rear udder attachment (r =0,20), P ˂ 0,05–0,001; narrow-body and wide-body types – with chest width (r=0,30) and rump width (r=0,23), P˂0,05–0,01. Linear type trait evaluation of cows depends on the body build. The strength and direction of the correlations between types of body build and linear traits showed that the most informative is the classification of the body build by low-, mid- and high-capacity according to Chernenko – on the average η2x=17,5 %. The less informative – by narrow-body and wide-body types according to Kolesnik – η2x=7,6 %. The classification of cows on delicate-rough, narrow-body and wide-body types (according to Kolesnik) according to informativeness and reliability can have the intermediate position – η2x=10,0–11,5 %. The strongest influence on the body build has the cows’ height (η2x=27,9 % on average for all studied types of body build), chest width (η2x=33,5 %), body depth (η2x=21,8 %), rump width (η2x=24,1 %) and rear legs (η2x=18,7 %). Key words: cows, linear type trait evaluation, body build, correlation, power of influence.


Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Aneta Jończy ◽  
Rafał Mazgaj ◽  
Rafał Radosław Starzyński ◽  
Piotr Poznański ◽  
Mateusz Szudzik ◽  
...  

In mammals, 2 × 1012 red blood cells (RBCs) are produced every day in the bone marrow to ensure a constant supply of iron to maintain effective erythropoiesis. Impaired iron absorption in the duodenum and inefficient iron reutilization from senescent RBCs by macrophages contribute to the development of anemia. Ferroportin (Fpn), the only known cellular iron exporter, as well as hephaestin (Heph) and ceruloplasmin, two copper-dependent ferroxidases involved in the above-mentioned processes, are key elements of the interaction between copper and iron metabolisms. Crosslinks between these metals have been known for many years, but metabolic effects of one on the other have not been elucidated to date. Neonatal iron deficiency anemia in piglets provides an interesting model for studying this interplay. In duodenal enterocytes of young anemic piglets, we identified iron deposits and demonstrated increased expression of ferritin with a concomitant decline in both Fpn and Heph expression. We postulated that the underlying mechanism involves changes in copper distribution within enterocytes as a result of decreased expression of the copper transporter—Atp7b. Obtained results strongly suggest that regulation of iron absorption within enterocytes is based on the interaction between proteins of copper and iron metabolisms and outcompetes systemic regulation.


2004 ◽  
Vol 4 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Rute Cândida Pereira ◽  
Alcides da Silva Diniz ◽  
Luiz Oscar Cardoso Ferreira

The authors focus iron intake regulation in the body and the probable mechanisms related to iron absorption. They analyze the impact of iron absorption deficiency resulting in iron deficiency anemia, a public health issue of great impact in the world influencing child and maternal health risk increase. This paper aims at highlighting the problems affecting the uptake or inhibiting processes of iron absorption in an attempt to correlate information on conditioning factors and current findings. This study is a document based descriptive study comprising literature review. In food, iron has different forms, such as the heme and non-heme forms following different absorption pathways with different efficiency rates, depending on conditioning factors, such as diet profile, physiological aspects, iron chemical state, absorption regulation, transportation, storing, excretion and the presence of disease, They also discuss the current difficulties in dealing with iron nutritional deficiency in vulnerable groups, children and pregnant women, and focus data on iron consumption, adhesion to breast feeding and the frequency of prenatal care visits.


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