Study of Serum Hepcidin in Hereditary Hemolytic Anemias

Beshlawy, Amal El; Alaraby, Ibrahim; Kader, Mohamed Salah Eldin Mohamed Abdel; Ahmed, Dalia; Abdelrahman, Hossam E.M.

doi:10.3109/03630269.2012.721151

Cited by 23 publications

(19 citation statements)

References 26 publications

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“…For example, when a group of transfused β-thalassemia patients were compared to a group of SCD patients of similar age and equal mean total body iron loading (LIC), 20 to 30% of the thalassemia patients had cardiac dysfunction, gonadal failure, and growth delay whereas essentially none of the SCD patients had these problems [160]. This may be related to the lower levels of LPI [154] and relatively high hepcidin levels in SCD [161, 162]. …”

Section: Iron Toxicitymentioning

confidence: 99%

Physiology and pathophysiology of iron in hemoglobin-associated diseases

Coates

2014

Free Radical Biology and Medicine

145

118

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Iron overload and iron toxicity, whether because of increased absorption or iron loading from repeated transfusions, can be major causes of morbidity and mortality in a number of chronic anemias. Significant advances have been made in our understanding of iron homeostasis over the past decade. At the same time, advances in magnetic resonance imaging have allowed clinicians to monitor and quantify iron concentrations non-invasively in specific organs. Furthermore, effective iron chelators are now available, including preparations that can be taken orally. This has resulted in substantial improvement in mortality and morbidity for patients with severe chronic iron overload. This paper reviews the key points of iron homeostasis and attempts to place clinical observations in patients with transfusional iron overload in context with the current understanding of iron homeostasis in humans.

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Section: Iron Toxicitymentioning

confidence: 99%

Physiology and pathophysiology of iron in hemoglobin-associated diseases

Coates

2014

Free Radical Biology and Medicine

145

118

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“…30 Physiologically, cellular iron is exported by an iron export protein, ferroportin, which is negatively regulated by hepcidin. 31 In SCD patients, hepcidin levels can be either decreased 32 or increased. 33 We previously showed that expression of ferroportin inhibits HIV-1 replication and that hepcidin treatment increases intracellular iron and induces HIV-1 replication.…”

Section: Introductionmentioning

confidence: 99%

Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease

Kumari¹,

Ammosova²,

Diaz³

et al. 2016

Blood Advances

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The low incidence of HIV-1 infection in patients with sickle cell disease (SCD) and inhibition of HIV-1 replication in vitro under the conditions of low intracellular iron or heme treatment suggests a potential restriction of HIV-1 infection in SCD. We investigated HIV-1 ex vivo infection of SCD peripheral blood mononuclear cells (PBMCs) and found that HIV-1 replication was inhibited at the level of reverse transcription (RT) and transcription. We observed increased expression of heme and iron-regulated genes, previously shown to inhibit HIV-1, including ferroportin, IKBα, HO-1, p21, and SAM domain and HD domain-containing protein 1 (SAMHD1). HIV-1 inhibition was less pronounced in hepcidin-treated SCD PBMCs and more pronounced in the iron or iron chelators treated, suggesting a key role of iron metabolism. In SCD PBMCs, labile iron levels were reduced and protein levels of ferroportin, HIF-1α, IKBα, and HO-1 were increased. Hemin treatment induced ferroportin expression and inhibited HIV-1 in THP-1 cells, mimicking the HIV-1 inhibition in SCD PBMCs, especially as hepcidin similarly prevented HIV-1 inhibition. In THP-1 cells with knocked down ferroportin, IKBα, or HO-1 genes but not HIF-1α or p21, HIV-1 was not inhibited by hemin. Activity of SAMHD1-regulatory CDK2 was decreased, and SAMHD1 phosphorylation was reduced in SCD PBMCs and hemin-treated THP-1 cells, suggesting SAMHD1-mediated HIV-1 restriction in SCD. Our findings point to ferroportin as a trigger of HIV-1 restriction in SCD settings, linking reduced intracellular iron levels to the inhibition of CDK2 activity, reduction of SAMHD1 phosphorylation, increased IKBα expression, and inhibition of HIV-1 RT and transcription.

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“…The peptide hormone hepcidin inhibits release of iron from macrophages, entrecotes, and hepatocytes into the plasma via degradation of a transmembrane iron exporter, ferroportin (Moayedi et al, ; Thephinlap et al, ). It is suggested that globin chain impairment in β‐thalassemia major causes ineffective erythropoiesis, anemia, and increased erythropoietin production, which results in enhanced erythroferrone production, an erythroid‐derived hormone that reduces hepcidin synthesis in the liver (El Beshlawy, Alaraby, Abdel Kader, Ahmed, & Abdelrahman, ).…”

Section: Discussionmentioning

confidence: 99%

An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β‐thalassemia major patients: A double‐blind randomized controlled clinical trial

Mohammadi

Tamaddoni

Qujeq

et al. 2018

Phytotherapy Research

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This study investigated the effects of curcumin, the active polyphenol in turmeric, on iron overload, hepcidin level, and liver function in β-thalassemia major patients. This double-blind randomized controlled clinical trial was conducted on 68 β-thalassemia major patients. The subjects were randomly divided into 2 groups to receive either 500 mg curcumin capsules (total: 1,000 mg) twice daily or placebo for 12 weeks. Dietary intakes and biochemical variables including hemoglobin, transferrin saturation, total iron binding capacity, nontransferrin bound iron (NTBI), ferritin, hepcidin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed at the beginning and end of the trial. Curcumin significantly reduced serum levels of NTBI (2.83 ± 1.08 compared with 2.22 ± 0.97 μmol/L, p = .001), ALT (42.86 ± 11.15 compared with 40.60 ± 9.89 U/L, p = .018), and AST (49.45 ± 12.39 compared with 46.30 ± 10.85 U/L, p = .002) at the end of the study. Based on analysis of covariance, a significant decrease was also observed in levels of NTBI (2.22 ± 0.97 vs. 2.55 ± 0.94 μmol/L, p = .026), ALT (40.60 ± 9.89 vs. 45.01 ± 10.42 U/L, p = .004), and AST (46.30 ± 10.85 vs. 50.99 ± 9.36 U/L, p = .009) in curcumin group in comparison with placebo group. There were no significant changes in hepcidin and other variables in any of the 2 groups. Curcumin administration alleviated iron burden and liver dysfunction by reducing NTBI, ALT, and AST levels in patients with β-thalassemia major.

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Study of Serum Hepcidin in Hereditary Hemolytic Anemias

Cited by 23 publications

References 26 publications

Physiology and pathophysiology of iron in hemoglobin-associated diseases

Physiology and pathophysiology of iron in hemoglobin-associated diseases

Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease

An investigation of the effects of curcumin on iron overload, hepcidin level, and liver function in β‐thalassemia major patients: A double‐blind randomized controlled clinical trial

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