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Intestinal Iron Absorption (intestinal + iron_absorption)

Distribution by Scientific Domains
Medical Sciences81%

Selected Abstracts

The Effects of Inhibition of Haem Biosynthesis by Griseofulvin on Intestinal Iron Absorption

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2004
Abas H. Laftah
Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3,7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption. [source]

Effect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorption

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2004
G. O. Latunde-Dada
Abstract Background, Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of ,-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. Design, We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. Results, While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 µmoles kg,1 body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. Conclusions, The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important. [source]

Impaired intestinal iron absorption in Crohn's disease correlates with disease activity and markers of inflammation

INFLAMMATORY BOWEL DISEASES, Issue 12 2006
Gaith Semrin MD
Abstract Background: Anemia in patients with Crohn's disease (CD) is a common problem of multifactorial origin, including blood loss, malabsorption of iron, and anemia of inflammation. Anemia of inflammation is caused by the effects of inflammatory cytokines [predominantly interleukin-6 (IL-6)] on iron transport in enterocytes and macrophages. We sought to elucidate alterations in iron absorption in pediatric patients with active and inactive CD. Methods: Nineteen subjects with CD (8 female, 11 male patients) were recruited between April 2003 and June 2004. After an overnight fast, serum iron and hemoglobin levels, serum markers of inflammation [IL-6, C-reactive protein (CRP), and erythrocyte sedimentation rate], and a urine sample for hepcidin assay were obtained at 8 am. Ferrous sulfate (1 mg/kg) was administered orally, followed by determination of serum iron concentrations hourly for 4 hours after the ingestion of iron. An area under the curve for iron absorption was calculated for each patient data set. Results: There was a strong inverse correlation between the area under the curve and IL-6 (P = 0.002) and area under the curve and CRP levels (P = 0.04). Similarly, the difference between baseline and 2-hour serum iron level (,[Fe]2hr) correlated with IL-6 (P = 0.008) and CRP (P = 0.045). When cutoff values for IL-6 (>5 pg/mL) and CRP (>1.0 mg/dL) were used, urine hepcidin levels also positively correlated with IL-6 and CRP levels (P = 0.003 and 0.007, respectively). Conclusions: Subjects with active CD have impaired oral iron absorption and elevated IL-6 levels compared with subjects with inactive disease. These findings suggest that oral iron may be of limited benefit to these patients. Future study is needed to define the molecular basis for impaired iron absorption. [source]

Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009
Nilesh R. Ghugre
Patients with sickle cell disease (SCD) appear to be at lower risk of endocrinopathies and cardiac dysfunction than those with thalassemia major (TM). Circulating redox active iron is lower in these patients, possibly due to increased systemic inflammation and circulating cytokines. Hepcidin synthesis is upregulated during chronic inflammation, reducing intestinal iron absorption and promoting retention of iron in the reticuloendothelial cells. Hence, we hypothesized that livers of patients with SCD would exhibit greater iron deposition in sinusoidal spaces relative to hepatocytes and less in portal tracts when compared to patients with TM. To test this hypothesis, iron scoring analysis was performed on 70 clinically indicated liver biopsy specimens from children and young adults with the two syndromes. Sinusoidal scores were lower in around 1 of 4 patients with TM but the relative iron loading in hepatocytes, and portal tracts was identical in both diseases. Sinusoidal iron burdens saturated at low hepatic iron concentration (HIC) while hepatocyte and portal iron depots increased proportionally to HIC. Liver fibrosis was increased in patients with TM regardless of their chronic hepatitis status. Overall, liver iron distribution was relatively insensitive to differences in disease type and to the presence or absence of hepatitis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

The Effects of Inhibition of Haem Biosynthesis by Griseofulvin on Intestinal Iron Absorption

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2004
Abas H. Laftah
Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3,7 days. Urinary porphobilinogen levels also showed a similar trend. In vivo intestinal iron absorption was significantly reduced (P<0.05) in experimental mice, mainly due to reduction in the transfer of 59Fe from the enterocytes to the portal circulation. In vitro studies using isolated duodenal fragments also exhibited marked decreases in both iron uptake and Fe (III) reduction. Changes in mucosal Divalent Metal Transporter 1 (DMT-1), Dcytb and Ireg1 (iron regulated protein 1) mRNA levels paralleled the changes in iron absorption. The reduction in iron absorption after griseofulvin treatment was normalised when mice were simultaneously injected with haem-arginate. These data support the hypothesis that intermediates in haem biosynthesis, particularly 5-aminolaevulinic acid, regulate intestinal iron absorption. [source]

Regulatory mechanisms of intestinal iron absorption,Uncovering of a fast-response mechanism based on DMT1 and ferroportin endocytosis

BIOFACTORS, Issue 2 2010
Marco T. Núńez
Abstract Knowledge on the intestinal iron transport process and the regulation of body iron stores has greatly increased during the last decade. The liver, through the sensing of circulating iron, is now recognized as the central organ in this regulation. High iron levels induce the synthesis of hepcidin, which in turn decreases circulating iron by inhibiting its recycling from macrophages and its absorption at the intestine. Another mechanism for the control of iron absorption by the enterocyte is an active Iron Responsive Element (IRE)/Iron Regulatory Protein (IRP) system. The IRE/IRP system regulates the expression of iron uptake and storage proteins thus regulating iron absorption. Similarly, increasing evidence points to the transcriptional regulation of both divalent metal transporter 1 (DMT1) and ferroportin expression. A new mechanism of regulation related to a phenomenon called the mucosal block is starting to be unveiled. The mucosal block describes the ability of an initial dose of ingested iron to block absorption of a second dose given 2,4 h later. Here, we review the mechanisms involved in the expression of DMT1 and ferroportin, and present recent evidence on the molecular components and cellular processes involved in the mucosal block response. Our studies indicate that mucosal block is a fast-response endocytic mechanism destined to decrease intestinal iron absorption during a high ingest of iron. [source]

Role of interleukin-6 in hypoxic regulation of intestinal iron absorption

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005
Kishor B. Raja
Summary The regulation of intestinal iron absorption is not fully understood. Hepcidin, a liver-produced peptide, has recently been identified as a negative regulator of iron absorption in various conditions associated with altered iron metabolism (e.g. inflammation, anaemia, hypoxia). It is not clear whether these perturbants share a common signalling pathway. In this study, the importance of the cytokine interleukin-6 (IL-6) was investigated in the hypoxic mouse model. Hypoxia was associated with increased levels of circulating IL-6, decreased liver hepcidin mRNA and increased iron absorption (especially MT). A significant positive correlation existed between the total iron uptake and IL-6 levels in circulation. IL-6 per se, though inducing hepcidin mRNA, failed to affect basal iron absorption. The adaptive response to absorption following the hypoxic exposure was, however, more prominent if mice had been treated concurrently with IL-6. This enhancement in absorption occurred even though hepcidin mRNA was not significantly changed. Similar prominent responses were seen with both human and mouse IL-6. Anti-IL-6 antiserum normalised iron absorption in mice exposed to hypoxia, because of a reduction in the MT. These data indicate that IL-6 can influence iron absorption (especially MT) during the hypoxic exposure, but via a mechanism independent of hepcidin. [source]