Dataset Information

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

ABSTRACT:

Purpose

Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.

Methods

Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.

Results

Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.

Conclusions

Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.

SUBMITTER: Lin D

PROVIDER: S-EPMC3679136 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

Lin Dong D Ding Jing J Liu Jian-Ying JY He Yi-Feng YF Dai Zhi Z Chen Cai-Zhong CZ Cheng Wei-Zhong WZ Zhou Jian J Wang Xin X

PloS one 20130611 6

<h4>Purpose</h4>Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron ...[more]

PMID: 23776499

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Project description:Astrocytes are the most abundant glial cells in the central nervous system (CNS). As indispensable elements of the neurovascular unit, they are involved in the inflammatory response and disease-associated processes. Alpha-synuclein (?-syn) is released into the extracellular space by neurons and can be internalized by adjacent astrocytes, which activates glial cells to induce neuroinflammation. We were interested in whether astrocyte-mediated neuroinflammation is modulated by intracellular iron status and extracellular ?-syn. Our results showed that recombinant ?-syn (1 ?g/ml and 5 ?g/ml) treatment for 24 h did not affect the expression of the iron transporters divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), nor those of iron regulatory protein (IRP) 1 or IRP2. Several proinflammatory cytokines, including tumor necrosis factor-? (TNF-?), interleukin (IL)-1?, and IL-6 exhibited up-regulated mRNA levels in 5 ?g/ml ?-syn-treated astrocytes. TNF-? release was increased, indicating that inflammatory responses were triggered in these cells. Pretreatment with the iron-overload reagent ferric ammonium citrate (FAC, 100 ?mol/L) for 24 h had no effects on mRNA levels and release of proinflammatory cytokines. Inflammatory responses triggered by ?-syn were not affected by iron overload. The iron chelator desferrioxamine (DFO, 100 ?mol/L) exerted suppressive effects on TNF-? mRNA levels, although no change was observed for TNF-? release. Hepcidin mRNA levels were down-regulated significantly in astrocytes co-treated with FAC and ?-syn, although independent treatment with either FAC or ?-syn did not alter hepcidin levels. In contrast, hepcidin mRNA levels were up-regulated in DFO and ?-syn co-treated cells. As expected, ferritin protein levels were up-regulated or down-regulated with FAC or DFO treatment, respectively. Following the up-regulation of ferritin mediated by ?-syn, hepcidin-to-ferritin levels were indicative of modulatory effects in ?-syn-treated astrocytes with altered iron status. Therefore, we propose that the hepcidin-to-ferritin ratio is indicative of a detrimental response in primary cultured astrocytes experiencing iron and extracellular ?-syn.

Dataset Information

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

Purpose

Methods

Results

Conclusions

Publications

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

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