Red Blood Cell Hemolysis and Suppression of Erythropoiesis Strongly Upregulate mRNA for Iron Binding Lipocalin (NGAL/24p3) in the Liver.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3201-3201
Author(s):  
Emanuel Necas ◽  
Martin Vokurka ◽  
Jan Krijt

Abstract A member of the lipocalin family of proteins, NGAL/24p3, was demonstrated to bind iron and was suggested to participate in a non-transferrin dependent iron transport mechanism capable to deliver iron to the cytoplasm (Kaplan 2002, Yang et al. 2003). Therefore, we have studied mRNA for NGAL/24p3 levels in the liver tissue during its loading with iron released from senescent and damaged red blood cells. Red blood cell hemolysis was induced in mice by administration of phenylhydrazine (PHZ). Suppression of iron reutilization for erythropoiesis was achieved by a total body sublethal irradiation (5 Gy). Samples of liver tissue were collected 16 hrs or 48 hrs after PHZ and 40 hrs after irradiation. Combined treatment consisted from irradiation followed by PHZ administration 40 hrs later. The irradiation suppressed 24 hrs incorporation of 59Fe into blood from 46,5 % in controls to 1.2 % in irradiated mice, indicating a significant suppression of erythropoiesis. PHZ administration alone decreased hematocrit from 44.7 % to 38.7 %, reflecting degree of the red blood cell hemolysis. The combined treatment by irradiation and PHZ resulted in the elevation of the liver iron content from 43.8 to 106.7 micrograms/g wet tissue 16 hours after PHZ, indicating a significant loading of the liver tissue with iron. All these treatments increased mRNA for NGAL/24p3 levels as determined by real-time PCR, significantly. After the combined treatment the increase reached almost three orders of magnitude. We further compared the response of NGAL/24p3 mRNA to the response of hepcidin and transferrin-1 receptor (TfR-1) mRNAs, both known to be sensitive to the liver iron content. Hepcidin mRNA increased significantly after the treatment with irradiation, PHZ, or combination of irradiation and PHZ but the increase was less pronounced compared to that of NGAL/24p3 mRNA. TfR-1 mRNA significantly decreased 48 hours after the combined treatment only. As an indicator of the acute phase response, the mRNA for interleukin-6 was determined and it did not change after the treatments used. The results demonstrate that mRNA for the putative iron transport molecule NGAL/24p3 was strongly upregulated by experimental maneuvers that lead to accumulation of iron in the liver tissue.

2019 ◽  
Vol 44 (9) ◽  
pp. 3058-3068 ◽  
Author(s):  
Juan S. Calle-Toro ◽  
Christian A. Barrera ◽  
Dmitry Khrichenko ◽  
Hansel J. Otero ◽  
Suraj D. Serai

2015 ◽  
Vol 26 (2) ◽  
pp. 233-234 ◽  
Author(s):  
Nejat Akar ◽  
Yasemin Ardçoğlu ◽  
Zeki Öktem ◽  
Nuran Erduran ◽  
Ibrahim C. Haznedaroglu

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Junbei Bai

Objective To observe the national elite male rowers blood, red blood cell activity and serum copper, zinc, calcium, magnesium and iron content of the five elements, and compared with the ordinary people. Aimed to investigate the between athletes, athletes and ordinary differences between the two sets of indicators and to explore the impact of element contents in red blood cell activity and five factors. Trying to bring two sets of indicators and specific combining ability, used in training on the monitoring function, and for the future to provide some references for further study. Methods It was included 22 athletes and 22 ordinary men, as the research object, in the collection of blood, measuring red blood cell activity in the blood content of the five elements, simultaneous measurement of physical indicators , will be doing all the data at the differences between the two groups compared to the group to do correlation analysis. The recent record of 2000m, 6000m rowing Dynamometer test results, and red blood cell activity associated with the five elements of content analysis. Results 1. Athletes indicators related to aerobic exercise were significantly higher than ordinary people. The white blood cells of athletes group were average.It shows that athletes have high aerobic capacity, while white blood cells are more stable than normal people. The members of the national rowing men's iron, magnesium content was significantly higher than ordinary group, the iron content is higher than the normal reference value; blood calcium levels were significantly lower than ordinary people, and lower than the normal reference value. The total number of red blood cells and the number of living cells was very significant positive correlation in two groups subjects; Red blood cell activity and red blood cell diameter is proportional, and red blood cell roundness in inverse proportion to the relationship; from this experiment a special ability to see red blood cell activity and there is no correlation. In both groups, hemoglobin was positively correlated with iron content, while iron was positively correlated with copper content. Conclusions 1. Increasing the number and volume of red blood cells can effectively increase the activity of red blood cells; red blood cell activity has no correlation with specific ability, and can not be used as an indicator to determine specific ability. The content of iron and magnesium in rowers is higher than that in ordinary people, which indicates that the adjustment of aerobic capacity and nerve control is very effective. The lower calcium content indicates that the injury caused by calcium loss should be prevented and the urgency of calcium supplementation should be emphasized. In training, we should pay attention to increasing hemoglobin content and aerobic capacity by supplementing iron. We can further consider the effect of supplementing copper to promote iron supplementation.


Hematology ◽  
2003 ◽  
Vol 8 (6) ◽  
pp. 429-432 ◽  
Author(s):  
Pradyumna D. Phatak ◽  
James C. Barton

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Joel Marmur ◽  
Soheir Beshara ◽  
Gösta Eggertsen ◽  
Liselotte Onelöv ◽  
Nils Albiin ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3825-3825
Author(s):  
Nelson Hamerschlak ◽  
Laercio Rosemberg ◽  
Alexandre Parma ◽  
Fernanda F. Assir ◽  
Frederico R. Moreira ◽  
...  

Abstract Magnetic Ressonance Imaging (MRI) using T2 star (T2*) tecnique appears to be a very useful method for monitoring iron overload and iron chelation therapy in thalassaemia. In Brazil, we have around 400 thalassaemic major patients all over the country. They were treated with hipertransfusion protocols and desferroxamine and/or deferiprone chelation. We developed a cooperative program with the Brazilian Thalassaemic Patients Association (ABRASTA) in order to developT2* tecnique in Brazil to submit brazilian patients to an annual iron overload monitoring process with MRI.. We performed the magnetic ressonance T2* using GE equipment (GE, Milwaukee USA), with validation to chemical estimation of iron in patients undergoing liver biopsy. Until now, 60 patients were scanned, median age=23,2 (12–54); gender: 18 male (30%) and 42 female (70%). The median ferritin levels were 2030 ng/ml (Q1=1466; Q3=3296). As other authors described before, there was a curvilinear inverse correlation between iron concentration by biopsy, liver T2*(r=0,92) and also there were a correlation with ferritin levels. We also correlated myocardial iron measured by T2* with ventricular function.. As miocardial iron increased, there was a progressive decline in ejection fraction and no significant correlation was found between miocardial T2* and the ferritin levels. Liver iron content can be predicted by ferritin levels. On the other hand, cardiac disfunction is the most important cause of mortality among thalassaemic patients. Since Miocardio iron content cannot be predicted from serum ferritin or liver iron, and ventricular function can only detect those with advance disease, intensification and combination of chelation therapy, guided by T2* MRI tecnique should reduce mortality from the reversible cardiomyopathy among thalassaemic patients.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3493-3493
Author(s):  
Martin Wermke ◽  
Jan Moritz Middeke ◽  
Nona Shayegi ◽  
Verena Plodeck ◽  
Michael Laniado ◽  
...  

Abstract Abstract 3493 An increased risk for GvHD, infections and liver toxicity after transplant has been attributed to iron overload (defined by serum ferritin) of MDS and AML patients prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, the reason for this observation is not very well defined. Consequently, there is a debate whether to use iron chelators in these patients prior to allo-HSCT. In fact, serum ferritin levels and transfusion history are commonly used to guide iron depletion strategies. Both parameters may inadequately reflect body iron stores in MDS and AML patients prior to allo-HSCT. Recently, quantitative magnetic resonance imaging (MRI) was introduced as a tool for direct measurement of liver iron. We therefore aimed at evaluating the accurateness of different strategies for determining iron overload in MDS and AML patients prior to allo-HSCT. Serologic parameters of iron overload (ferritin, iron, transferrin, transferrin saturation, soluble transferrin receptor) and transfusion history were obtained prospectively in MDS or AML patients prior to allo-SCT. In parallel, liver iron content was measured by MRI according to the method described by Gandon (Lancet 2004) and Rose (Eur J Haematol 2006), respectively. A total of 20 AML and 9 MDS patients (median age 59 years, range: 23–74 years) undergoing allo-HSCT have been evaluated so far. The median ferritin concentration was 2237 μg/l (range 572–6594 μg/l) and patients had received a median of 20 transfusions (range 6–127) before transplantation. Serum ferritin was not significantly correlated with transfusion burden (t = 0.207, p = 0.119) but as expected with the concentration of C-reactive protein (t = 0.385, p = 0.003). Median liver iron concentration measured by MRI was 150 μmol/g (range 40–300 μmol/g, normal: < 36 μmol/g). A weak but significant correlation was found between liver iron concentration and ferritin (t = 0.354; p = 0.008). The strength of the correlation was diminished by the influence of 5 outliers with high ferritin concentrations but rather low liver iron content (Figure 1). The same applied to transfusion history which was also only weakly associated with liver iron content (t = 0.365; p = 0.007). Levels of transferrin, transferrin saturation, total iron and soluble transferrin receptor did not predict for liver iron concentration. Our data suggest that serum ferritin or transfusion history cannot be regarded as robust surrogates for the actual iron overload in MDS or AML patients. Therefore we advocate caution when using one of these parameters as the only trigger for chelation therapy or as a risk-factor to predict outcome after allo-HSCT. Figure 1. Correlation of Liver iron content with Ferritin. Figure 1. Correlation of Liver iron content with Ferritin. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3208-3208
Author(s):  
Aileen W. Zhen ◽  
Josephine Volovetz ◽  
Paula G. Fraenkel

Abstract Abstract 3208 Iron overload is an important cause of morbidity and death in patients with hemoglobinopathies, transfusion-dependent anemias, and hereditary hemochromatosis. As humans have no means of excreting iron, regulation of iron homeostasis depends on limiting intestinal iron absorption and optimizing iron release from macrophages to developing erythrocytes. Hepcidin, a peptide hormone produced in the liver, modulates intestinal iron absorption and macrophage iron release via effects on ferroportin. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. We conducted a small-scale chemical screen and found that the isoflavone genistein, a major dietary component of soybeans, enhanced Hepcidin transcript levels in zebrafish embryos. Furthermore genistein treatment increased Hepcidin transcript levels and Hepcidin promoter activity in human hepatocytes (HepG2 cells) in a Stat3 and Smad4-dependent manner. To evaluate genistein's effect in a mammalian model, we placed groups of 4 four-week old male C57BL/6 mice on an iron-sufficient, low soy diet (AIN93G containing 35 mg of iron/kg) supplemented with 0, 250, or 500 mg of genistein per kg of food for 7 weeks, and then sacrificed the animals for analysis. Plasma genistein levels (mean±SE) at the time of sacrifice were 0.015±0.015, 0.52±0.173, and 2.07±0.65 micromolar, respectively. Compared to mice not treated with genistein, the 250 mg/kg dose produced a significant increase in hepatic Hepcidin (HAMP1) transcript levels (1.49±0.10 vs 0.93±0.10, p=0.01), while the 500 mg/kg dose did not. Although liver iron content, spleen iron content, and weight gain were not significantly different among the groups, the ratio of Hepcidin expression to liver iron content was significantly increased in the animals treated with genistein 250 mg/kg compared to controls (0.013±0.0009 vs 0.0074±0.00068, p=0.0068). In conclusion, genistein is the first orally administered small molecule experimental drug shown to increase Hepcidin transcript levels in vivo. Future experiments will evaluate the effects of genistein on genetic models of iron overload syndromes. Disclosures: No relevant conflicts of interest to declare.


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