Hepcidin Levels Research Articles

Roles of ghrelin, hepcidin and HIF-2α in iron metabolism in iron deficiency anemia.

This study investigates the roles of HIF-2α, hepcidin, and ghrelin in iron deficiency anemia (IDA), the most widespread nutritional disorder globally. Fifty IDA patients (18-50years, BMI 19-25) and 40 healthy volunteers were studied. Hemoglobin, ferritin, hepcidin, HIF-2α, and ghrelin levels were analyzed. IDA patients showed lower hemoglobin, ferritin, hepcidin, and ghrelin levels than the control group, but HIF-2α levels were similar. Positive correlations were observed in both groups between hepcidin and HIF-2α (p < 0.001), hepcidin and ghrelin (p < 0.001), and HIF-2α and ghrelin (p < 0.001). Hemoglobin was correlated positively with HIF-2α, and ferritin was correlated positively with HIF-2α in the patient group. The study suggests that the low hepcidin levels in IDA patients enhance iron absorption. The lack of significant HIF-2α level differences may be due to the absence of chronic hypoxia in current hemoglobin levels of IDA patients. Moreover, the low ghrelin levels in patients and the correlations between ghrelin, hepcidin, and HIF-2α in both groups indicate their involvement in iron metabolism.

Measurement of serum hepcidin-25 by latex agglutination in healthy volunteers and patients with hematologic disorders.

Iron is an essential trace metal, vital for various physiologic processes, but excess levels can harm health. Maintaining iron homeostasis is critical, with hepcidin playing a key role. The isoform hepcidin-25 exerts the most significant influence on iron metabolism, making its serum levels a valuable diagnostic tool. However, mass-spectrometry and other conventional measurement methods can be difficult to perform, and some immunoassays lack reliability. In this study, we employed a recently developed latex agglutination method integrated with a readily available automated analyzer to quantify serum hepcidin-25 levels in both volunteers recruited from personnel of our hospital (n = 93) and patients with various hematological disorders (n = 112). Our findings unveiled a robust positive correlation between serum hepcidin-25 and ferritin, as well as C-reactive protein levels, in both volunteers and patients. Among the patients with hematological disorders, there was a noteworthy negative correlation between hepcidin-25 levels and hemoglobin concentrations, as well as reticulocyte counts. Interestingly, the hepcidin-25/ferritin ratio was remarkably low in patients with hemolytic anemia and myelodysplastic syndromes with ring sideroblasts. Our findings suggest that quantifying serum hepcidin-25 and the hepcidin-25/ferritin ratio using this method may be valuable for screening of hematopoietic diseases and other iron metabolism disorders.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9;p< 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2= 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2= 0.529, p = 0.002). We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Serum level of hepcidin in cirrhotic patients as a marker for hepatocellular carcinoma

BackgroundPeople all around the world are affected by primary liver cancers like hepatocellular carcinoma (HCC), which is usually associated with cirrhosis. Early HCC detection is crucial for better prognosis, but effective biomarkers are still needed. Hepcidin, a hormone-regulating iron homeostasis, has been implicated in liver diseases. In this study, blood hepcidin levels were evaluated in cirrhotic individuals as a possible biomarker for HCC.MethodsThere were three groups involved in this case-control study: cirrhotic patients with no HCC (group I), cirrhotic patients diagnosed with HCC (group II), and healthy controls (group III). Clinical and laboratory data, such as those from tests indicating the liver function, hepcidin levels, and imaging, were all analyzed using a number of statistical tests.ResultsWhen compared to those with cirrhosis, serum hepcidin levels were significantly lower in HCC patients, but there was no significant difference statistically between the two studies involved: cirrhotic groups and the controls. Serum alpha-fetoprotein (AFP) was also significantly greater in HCC patients.ConclusionsThe start and progression of liver diseases, such as HCC in cirrhotic people, appear to be influenced by hepcidin. It can be utilized as a potential HCC biomarker when cirrhotic liver is present, despite the fact that it cannot be used to diagnose cirrhosis by itself.

Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism.

The association of TMPRSS6 gene polymorphism with iron status in Egyptian children (a pilot study)

Several studies have shown association of single nucleotide polymorphisms (SNPs) of hepcidin regulatory pathways genes with impaired iron status. The most common is in the TMPRSS6 gene. In Africa, very few studies have been reported. We aimed to investigate the correlation between the common SNPs in the transmembrane protease, serine 6 (TMPRSS6) gene and iron indicators in a sample of Egyptian children for identifying the suitable candidate for iron supplementation.Patients and methods One hundred and sixty children aged 5–13 years were included & classified into iron deficient, iron deficient anemia and normal healthy controls. All were subjected to assessment of serum iron, serum ferritin, total iron binding capacity, complete blood count, reticulocyte count, serum soluble transferrin receptor and serum hepcidin. Molecular study of TMPRSS6 genotyping polymorphisms (rs4820268, rs855791 and rs11704654) were also evaluated.Results There was an association of iron deficiency with AG of rs855791 SNP, (P = 0.01). The minor allele frequency for included children were 0.43, 0.45 & 0.17 for rs4820268, rs855791 & rs11704654 respectively. Genotype GG of rs4820268 expressed the highest hepcidin gene expression fold, the lowest serum ferroportin & iron store compared to AA and AG genotypes (p = 0.05, p = 0.05, p = 0.03 respectively). GG of rs855791 had lower serum ferritin than AA (p = 0.04), lowest iron store & highest serum hepcidin compared to AA and AG genotypes (p = 0.04, p = 0.01 respectively). Children having CC of rs11704654 had lower level of hemoglobin, serum ferritin and serum hepcidin compared with CT genotype (p = 0.01, p = 0.01, p = 0.02) respectively.Conclusion Possible contribution of SNPs (rs855791, rs4820268 and rs11704654) to low iron status.

Influence of supplementation with iron and probiotic bacteria Lactobacillus plantarum and Lactobacillus curvatus on selected parameters of inflammatory state in rats on a high-fat iron-deficient diet.

A high-fat (HF) diet, diet iron deficiency and iron supplementation may affect inflammatory parameters. Probiotics influence both iron metabolism and inflammation. We compared the inflammatory state in rats on a HF iron-deficient diet receiving oral iron, Lactobacillus plantarum and Lactobacillus curvatus in different combinations. This was a two-stage experiment. In groups C (n = 8) and HF (n = 8), rats ate a control or HF diet, respectively, for 16 weeks. In the group HFDEF (n = 48), rats ate a HF iron-deficient diet for 8 weeks (first stage) and were subsequently divided into 6 groups (n = 8 each) receiving the following for a further 8 weeks (second stage): HFDEF - a HF iron-deficient diet; HFDEFFe - a HF iron-deficient diet with iron; HFDEFLp and HFDEFLc - a HF iron-deficient diet with L. plantarum or L. curvatus, respectively; and HFDEFFeLp and HFDEFFeLc - a HF iron-deficient diet with iron and L. plantarum or L. curvatus, respectively. Body composition analysis and blood sampling was performed. Markers of iron status and levels of total antioxidant status (TAS), C-reactive protein (CRP), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the blood. TAS was higher in the HFDEF group (756.57 ± 489.53 ng mL-1) versus the HFDEFLc group (187.04 ± 47.84 ng mL-1; P = 0.022). No more differences were found between groups, or in TAS, CRP, TNF-α and IL-6 concentrations. Also, no differences were found between groups for alanine and aspartate aminotransferases, glucose, total cholesterol, low- and high-density lipoproteins and triglycerides. TAS level was positively correlated with ferritin concentration, IL-6 with TAS and TNF-α with hepcidin level. Supplementation with L. plantarum, L. curvatus and iron in combinations exerts no influence on inflammatory status, lipid profile, hepatic function and serum fasting glucose in rats on a HF iron-deficient diet. © 2024 Society of Chemical Industry.

Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.

In clinics, hepcidin levels are elevated in various anemia-related conditions, particularly in iron-refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron-refractory anemia, the potential effect of hypoxia and pharmacologically-mimetic drug FG-4592 (Roxadustat) are evaluated, a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor, on mouse models of iron-refractory iron-deficiency anemia (IRIDA), anemia of inflammation and 5-fluorouracil-induced chemotherapy-related anemia. The potent protective effects of both hypoxia and FG-4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG-4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin-activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5-fluorouracil-induced anemia, which can not be rescued by FG-4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia-related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

The Role of Hepcidin in Myelodysplastic Syndromes (MDS): A Systematic Review of Observational Studies.

Iron overload emerges as a serious complication in myelodysplastic syndromes (MDS), particularly associated with frequent transfusions during the course of the disease. The discovery and description of hepcidin's mechanisms of action have contributed to a deeper understanding of iron metabolism. The existing literature reports a potential role of hepcidin in MDS, yet these data are fragmented and presented in an unstructured, somewhat chaotic manner. Hence, to address the existing data, we performed a systematic review of observational studies examining hepcidin levels in MDS. An extensive review of three bibliographic databases (Pubmed, Web of Science, and Scopus) enabled us to identify 12 observational studies. These studies focused primarily on adult patients with low-risk MDS who underwent transfusions and chelation therapy. An in-depth analysis of these manuscripts led to four main conclusions: (1) although high serum hepcidin levels are associated with MDS, most studies generally have not found a significant difference in these levels between patients and healthy individuals; (2) serum hepcidin levels are specific to MDS type; (3) serum hepcidin levels in MDS are strongly associated with transfusions and the genetic status of patients; and (4) high-risk MDS is associated with high serum hepcidin levels. While we have furnished a comprehensive summary of the significance of hepcidin in MDS, there are still gaps that future research should address. This pertains primarily to the capacity of hepcidin in predicting adverse outcomes for MDS patients and evaluating the efficacy of chelation therapy or the need for transfusion.

Riboflavin alleviates fluoride-induced ferroptosis by IL-17A-independent system Xc−/GPX4 pathway and iron metabolism in testicular Leydig cells

Fluoride is widely found in groundwater, soil, animal and plant organisms. Excessive fluoride exposure can cause reproductive dysfunction by activating IL-17A signaling pathway. However, the adverse effects of fluoride on male reproductive system and the mechanisms remain elusive. In this study, the wild type and IL-17A knockout C57BL/6J mouse were treated with 24 mg/kg·bw·d sodium fluoride and/or 5 mg/kg·bw·d riboflavin-5′-phosphate sodium for 91 days. Results showed that fluoride caused dental fluorosis, increased the levels of ROS in testicular Leydig cells and GSSG in testicular tissue, and did not affect the iron and serum hepcidin levels in testicular tissue. Riboflavin alleviated above adverse changes, whereas IL-17A does not participate in the oxidative stress-mediated reproductive toxicity of fluoride. Based on this, TM3 cells were used to verify the injury of fluoride on Leydig cells. Results showed that fluoride increased mRNA levels of ferroptosis marker SLC3A2, VDAC3, TFRC, and SLC40A1 and decreased Nrf2 mRNA levels in TM3 cells. The ferroptosis inhibitor Lip-1 and DFO were used to further investigate the relationship between male reproductive toxicity and ferroptosis induced by fluoride. We found that the fluoride-induced decrease in cell viability, increase in xCT, TFRC, and FTH protein expression, and decrease in GPX4 protein expression, can all be rescued by Lip-1 and DFO. Similar results were also observed in the riboflavin treatment group. Moreover, riboflavin mitigated fluoride-induced increases in ROS levels and SLC3A2 protein levels. In all, our work revealed that riboflavin inhibited ferroptosis in testicular Leydig cells and improved the declined male reproductive function caused by fluoride. This study provides new perspectives for revealing new male reproductive toxicity mechanisms and mitigating fluoride toxicity damage.

Acute and Chronic Effects of Interval Aerobic Exercise on Hepcidin, Ferritin, and Liver Enzymes in Adolescents With Beta-Thalassemia Major.

This study aimed to determine the acute and chronic effects of interval aerobic exercise on hepcidin, ferritin, and liver enzymes in adolescents with beta-thalassemia major. Twenty-six beta-thalassemia major adolescents referred to the Thalassemia Clinic and Research Center were selected as study participants and randomly divided into control (n = 13) and training (n = 13) groups. Participants performed 3 sessions per week for 45minutes in each session for 8 weeks of aerobic interval exercise with an intensity of 50% to 65% of the heart rate reserve. Blood samples were taken before, immediately after the exercise session, and 48hours after the last training session, and liver enzymes aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), ferritin, and hepcidin were evaluated. The results showed a decrease in aspartate aminotransferase, ALT, ALP, ferritin, and hepcidin levels due to 8 weeks of aerobic interval training (P = .14, P = .97, P = .03, P < .001, P < .001; respectively). Intergroup changes in all variables except ALT and hepcidin were significant (P < .05). Besides, acute aerobic exercise increased levels of aspartate aminotransferase, ALT, ferritin, and hepcidin (P = .04, P = .52, P < .001, P < .001; respectively), whereas ALP levels decreased (P < .001). In addition, changes in ALP and hepcidin levels were significant between the 2 groups (P = .05, P < .001; respectively). Based on the study's results, it can be concluded that 8 weeks of aerobic interval training can decrease ferritin and hepcidin levels, but acute aerobic exercise increases them.

Molecular characterization of HAMP rs10421768 gene and phenotypic expression of hepcidin; a case-control study among sickle cell anaemia patients in Ghana.

The sporadic nature of blood transfusion therapy coupled with the alteration of HAMP genes may exacerbate the risk of iron burden in sickle cell anaemia (SCA) patients. The study determined the polymorphic distribution of the HAMP promoter gene rs10421768 and hepcidin levels in SCA patients. Sixty participants aged ≥12years [45 SCA patients and 15 controls (HbA)] were recruited from 15th March, 2023 to 20th July, 2023 for a case-control study at Methodist Hospital Wenchi, Ghana. Complete blood count and hepcidin levels assessment were done using haematology analyzer and ELISA, respectively. Genomic DNA was extracted using the Qiagen Kit, and HAMP gene rs10421768 (c.-582 A>G) was sequenced using the MassARRAY method. Data were analysed using SPSS version 26.0. The frequencies of the HAMP promoter rs10421768 genotypes AA, AG, and GG were 64.4%, 33.3%, and 2.2% in SCA patients, and 86.7%, 13.3%, and 0% in the controls, respectively. Serum hepcidin levels were significantly higher among controls than cases [204.0 (154.1-219.3) vs 150.2 (108.1-195.6)μg/L, p<0.010]. Participants with HAMP rs10421768 homozygous A genotype had higher serum levels of hepcidin compared with those in the wild genotypes (AG/GG) group [(188.7 (130.9-226.9) vs 136.8 (109.7-157.8)μg/L, p<0.016]. Disease severity and blood cell parameters were not associated with the HAMP variants (p>0.05). The HAMP promoter rs10421768 AA genotype has the highest frequency of distribution and the GG genotype with the least distribution. Participants with HAMP rs10421768 G allele (c.-582A>G) had reduced levels of hepcidin. HAMP rs10421768 genotypes had no association with blood cell parameters and disease severity. The HAMP rs10421768 genotypes may influence serum levels of hepcidin. Further study is required to elucidate the potential effect of the G allele on hepcidin transcription.

High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload.

Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ГЕПСИДИНА В РЕГУЛЯЦИИ ОБМЕНА ЖЕЛЕЗА У ПАЦИЕНТОВ С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМ

Introduction. Anemia in juvenile idiopathic arthritis (JIA), as a rule, has a multifactorial genesis, which is based on an immune-mediated mechanism: cytokines during inflammation cause changes in iron metabolism, which leads to changes in the production of red blood cells and their precursors, reticulocytes; An increase in hepcidin content causes disturbances in iron metabolism. The purpose of the study was to study hepcidin levels in patients with JIA and determine its prognostic value for the development of anemia. Material and methods. A total of 65 patients with JIA who were undergoing inpatient treatment at the 2nd State Children's Clinical Hospital in Minsk were examined. All patients underwent a general blood test using a hematological analyzer “Sysmex XS-800i” (Japan) with determination of erythrocyte, reticulocyte, and platelet parameters. A biochemical blood test included determination of iron metabolism indicators. The enzyme immunoassay method was used to study the content of cytokines: interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-1β (IL-1β) and γ-interferon (γ-IFN). Results. All patients were divided into two groups according to the median hepcidin value. The first group, in which the values were less than 4760.0 pg/ml, included 31 patients, the second group, in which the values were more than 4760.0 pg/ml, included 34 patients. An increase in hepcidin content was accompanied by an increase in the incidence of anemia (χ² = 4.55; p = 0.03). Based on the results of the Pearson correlation analysis (r), a number of statistically significant relationships between the concentration of hepcidin and the level of IL-6 were identified (r = 0.27; p &lt; 0.05); hemoglobin (r= - 0.28; p&lt;0.05); hemoglobin content in the erythrocyte (r = - 0.29; p &lt; 0.05 and erythropoietin (r = 0.32; p &lt; 0.05). Conclusions. In children with juvenile idiopathic arthritis, increased levels of hepcidin in the blood are accompanied by an increased risk of developing anemia. The earliest markers of the development of this anemia are a decrease in the hemoglobin content in the erythrocyte, a decrease in the average volume of the erythrocyte, and an increase in the synthesis of immature forms of reticulocytes. Hepcidin acts as a marker of both the activity of the inflammatory process in children with JIA and affects the distribution of iron between its storage and the functionally active pool.

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin.

Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.

Lipopolysaccharide-Induced pregnant mice had decreased serum iron while maintaining hepcidin level and Hamp1 mRNA expression &amp;lrm;

Lipopolysaccharide-Induced pregnant mice had decreased serum iron while maintaining hepcidin level and Hamp1 mRNA expression &amp;lrm;

Potential Association of Serum Hepcidin, hs-CRP and Iron Status Levels in Hemodialytic Patients

Patients on hemodialysis (HD) are usually anemic because of defective erythropoiesis. Hepcidin is a polypeptide that regulates iron homeostasis and could indicate functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in assessing a patient's response to erythropoietin (EPO). The present study was directed to investigate serum levels of hepcidin, iron status, and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. Forty-two patients of both sexes on maintenance HD and EPO therapy were enrolled; 42 age and sex-matched healthy subjects were included as controls. Laboratory tests were performed, including complete blood count, serum hepcidin, total iron binding capacity (TIBC), serum ferritin, serum iron, and CRP. Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (18.2 \(\pm\) 2.8 ng/mL and 8.5 \(\pm\) 2.3 ng/mL, respectively P = 0.000). The hemoglobin, hematocrit, serum iron, TIBC, and transferrin saturation levels in the patient group were significantly lower than in the control group. Higher hepcidin levels were found in EPO non-responders (19.6 (\pm) 2.4 ng/mL), while lower levels (16.9 \(\pm\) 2.5 ng/mL) were seen in responders (P = 0.001). A positive and significant correlation was observed between the values of serum hepcidin and CRP. Our study indicates that higher hepcidin levels are found in ESRD patients on HD and in those not responding to EPO. Our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases and EPO resistance.

The Effect of Treatment on Weight Gain in Iron Deficiency Anemia and Its Association with Ghrelin and Hepcidin Levels

Aim: Although loss of appetite in iron deficiency anemia (IDA) and weight gain during treatment are common complaints, there are very few studies in adults. This study aimed to determine the levels of ghrelin, one of the appetite-related hormones, and hepcidin, one of the main regulators of iron metabolism, in IDA, and to examine the effects of treatment on weight gain and the levels of these hormones.&#x0D; Material and Methods: Eighty-seven adult patients with IDA and a control group of 50 healthy volunteers were included in the study. Anthropometric measurements and blood samples were obtained from the patient and control groups before treatment, and repeated after treatment in the IDA group.&#x0D; Results: No significant difference was found in terms of weight, body mass index (BMI), and waist-to-hip ratio between groups but there was a significant increase in weight and BMI, in the patient group after treatment (both p

Role of serum hepcidin as a marker of iron overload in beta thalassemia major

Background: Beta thalassemia major (BTM) is the most common hemolytic anemia. Regular blood transfusion is a basic treatment modality, recurrent blood transfusion which leads to iron overload and its complications. Hepcidin hormone is found to be a key regulator of iron homeostasis and is significantly increased in children of BTM with iron overload. The main objective of the study is to find out the role of serum hepcidin as a potential marker of iron overload in children with BTM, and to correlate the relationship between serum hepcidin and serum ferritin level in BTM children. Methods: This was a hospital based prospective observational study conducted at Indira Gandhi institute of child health for 12 months from January 2019 to December 2019. Included 100 children between age group of 2 months to 18 years diagnosed with BTM on blood transfusion and 50 age and sex matched healthy controls. Results: In the study group 70% children had &gt;5 transfusions. The median serum hepcidin level (2.354 ng/ml) was significantly higher among those with higher number of total transfusions (&gt;5 transfusions). In addition, hepcidin level showed good positive correlation with total number of transfusions (r=0.608, p&lt;0.001). Also, serum hepcidin showed positive correlation with serum ferritin levels with 87% sensitivity and 88% specificity which was statistically significant (r=0.749, p&lt;0.001). Conclusions: In the present study, BTM children who received &gt;5 transfusions serum hepcidin level was significantly elevated and serum hepcidin showed positive correlation with serum ferritin levels. Thus, hepcidin can be considered as a potential marker of iron overload in patients with BTM.

ACVR1: A Novel Therapeutic Target to Treat Anemia in Myelofibrosis.

Activin receptor type I (ACVR1) is a transmembrane kinase receptor belonging to bone morphogenic protein receptors (BMPs). ACVR1 plays an important role in hematopoiesis and anemia via the BMP6/ACVR1/SMAD pathway, which regulates expression of hepcidin, the master regulator of iron homeostasis. Elevated hepcidin levels are inversely associated with plasma iron levels, and chronic hepcidin expression leads to iron-restricted anemia. Anemia is one of the hallmarks of myelofibrosis (MF), a bone marrow (BM) malignancy characterized by BM scarring resulting in impaired hematopoiesis, splenomegaly, and systemic symptoms. Anemia and red blood cell transfusions negatively impact MF prognosis. Among the approved JAK inhibitors (ruxolitinib, fedratinib, momelotinib, and pacritinib) for MF, momelotinib and pacritinib are preferably used in cytopenic patients; both agents are potent ACVR1 inhibitors that suppress hepcidin expression via the BMP6/ACVR1/SMAD pathway and restore iron homeostasis/erythropoiesis. In September 2023, momelotinib was approved as a treatment for patients with MF and anemia. Zilurgisertib (ACVR1 inhibitor) and DISC-0974 (anti-hemojuvelin monoclonal antibody) are evaluated in early phase clinical trials in patients with MF and anemia. Luspatercept (ACVR2B ligand trap) is assessed in transfusion-dependent MF patients in a registrational phase 3 trial. Approved ACVR1 inhibitors and novel agents in development are poised to improve the outcomes of anemic MF patients.