Hepcidin in acute iron toxicity

Toledano, Michal; Kozer, Eran; Goldstein, Lee H.; Abu-Kishk, Ibrahim; Bar-Haim, Adina; Siman-Tov, Yariv; Rechavi, Moshe; Rechavi, Gideon; Weizer-Stern, Orly; Berkovitch, Matitiahu

doi:10.1016/j.ajem.2008.06.003

Cited by 7 publications

(6 citation statements)

References 26 publications

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“…Uric acid, as a chelating agent for iron ions, has been proven to be an efficient antioxidant in blood plasma [Davies et al, ; Mainous et al, ]. A previous study has demonstrated that, in rats receiving toxic doses of iron, the elevation of hepcidin expression in the liver was accompanied concomitantly by a significant increase of serum uric acid levels [Toledano et al, ]. It has been shown that in patients with iron overload, urea and ferritin, a protein that stores iron in the cell, levels correlated positively with uric acid levels [Barbosa et al, ].…”

Section: Discussionmentioning

confidence: 99%

Serum hepcidin levels in women infected with HIV-1 under antiviral therapy

2014

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Accumulating data suggest that iron may have a role in the regulation of HIV-infection. In the present study, we determined by radioimmunoassay the levels of hepcidin, a key regulator of iron homeostasis, in sera of 182 women infected with HIV-1 under highly active antiretroviral therapy (HAART). In the total cohort, hepcidin levels were lower in individuals infected with HIV than in controls (3.20 ± 3.06 vs. 5.68 ± 3.66 nmol/L, P = 0.009). Serum hepcidin concentrations were strongly correlated positively with iron, ferritin, urea, and uric acid. In the total cohort of patients with abnormal viral load and CD4 cell count <500 cells/mm(3) , a strong positive correlation was found between hepcidin and viral load. Hepcidin level was significantly higher in HIV-patients with high viremia than in patients with undetectable viral load. Iron level was significantly lower in HIV-patients with high viral load compared with patients with undetectable viral load. This study suggests that hepcidin controls serum iron, especially in response of iron utilization by HIV for viral replication. The possibility of using inhibitors of hepcidin expression as adjunct therapy for HIV-patients is discussed.

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Section: Discussionmentioning

confidence: 99%

Serum hepcidin levels in women infected with HIV-1 under antiviral therapy

2014

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“…12 These rat studies showed elevated concentrations of serum hepcidin and a higher concentration of hepcidin messenger RNA after administration of toxic doses of iron. 12,15 Hepcidin is the main iron-regulatory hormone, first described in 2000. 16 Hepcidin causes internalization and degradation of the ferroportin iron channels.…”

Section: Discussionmentioning

confidence: 99%

“…16 One would expect the hepcidin concentration to remain elevated for a longer period in moderate intoxication as occurred in our patient. 15 However, this can be explained by the enhanced elimination of iron by complexation with deferoxamine and the aforementioned rapid tissue uptake of iron from the circulation.…”

Section: Discussionmentioning

confidence: 99%

Iron autointoxication in a 16-year-old girl: a protective role for hepcidin?

Simonse

Valk-Swinkels²,

Veer³

et al. 2012

Ann Clin Biochem

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Intentional iron overdose appears to be an increasingly common form of attempted suicide. We present a case of iron overdose in a 16-year-old girl who was found unconscious in her bed and brought to our emergency department. The most remarkable diagnostic findings were the patient's comatose condition, divergent eye position and positive Babinski foot pad reflexes. Laboratory tests showed hyperglycaemia and mild metabolic acidosis. A computed tomography scan of the cerebrum showed no signs of intracerebral haemorrhage or elevated intracerebral pressure. Toxicology screening showed no use of acetaminophen, ethanol or drugs of abuse. The patient was stabilized and monitored on the intensive care ward. When she woke up, she confessed to having taken Fero-Gradumet(®). Retrospectively analysed, the serum iron concentration in the first blood sample (seven hours after ingestion) was 62 μmol/L which corresponds with moderate iron intoxication. The patient received whole bowel irrigation with 2 L polyethyleneglycol solution and de-ironing treatment with intravenous deferoxamine 20 mg/kg in eight hours. She was discharged from the hospital after three days in a good clinical condition. Retrospectively, serum hepcidin concentrations were determined and evaluated in conjunction with serum iron concentrations and the installed treatment. Before medical de-ironing interventions were started, we saw that the serum iron concentration in our patient was already declining. At the same time, we observed a sharp increase in the serum hepcidin concentration. After normalization of serum iron concentrations, hepcidin normalized as well.

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“…This phe-nomenon has been attributed to excess intracellular iron levels caused by elevated iron uptake capacity resulting from the upregulation of DMT1 expression in the iron-deficient state. Hepatic hepcidin synthesis was enhanced by increased iron storage in the liver, causing FPN degradation on the basolateral surface of epithelial cells (16,21,28,31).…”

Section: Fig 3 Levels Of Expression Of Duodenal Dmt1 (Ai: All Isofomentioning

confidence: 99%

Marginally excessive iron loading transiently blocks mucosal iron uptake in iron-deficient rats

Shinoda

Yoshizawa

Nozaki

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Regular “mucosal block” is characterized by decreased uptake of a normal iron load 3–72 h after the administration of excess iron (generally 10 mg) to iron-deficient animals. We found that short-acting mucosal block could be induced by much lower iron concentration and much shorter induction time than previously reported, without affecting levels of gene expression. A rapid endocytic mechanism was reported to decrease intestinal iron absorption after a high iron load, but the activating iron load and the time to decreased absorption were undetermined. We assessed the effects of 30–2,000 μg iron load on iron uptake in the duodenal loop of iron-deficient and iron-sufficient rats under anesthesia. One hour later, mucosal cellular iron uptake in iron-deficient rats administered 30 μg iron was 76.1%, decreasing 25% to 50.7% in rats administered 2,000 μg iron. In contrast, iron uptake by iron-sufficient rats was 63% (range 60.3–65.5%) regardless of iron load. Duodenal mucosal iron concentration was significantly lower in iron-deficient than in iron-sufficient rats. Iron levels in portal blood were consistently higher in iron-deficient rats regardless of iron load, in contrast to the decreased iron uptake on the luminal side. Iron loading blocked mucosal uptake of marginally excess iron (1,000 μg), with a greater effect at 15 min than at 30 min. The rapid induction of short-acting mucosal block only in iron-deficient rats suggests DMT1 internalization.

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Hepcidin in acute iron toxicity

Cited by 7 publications

References 26 publications

Serum hepcidin levels in women infected with HIV-1 under antiviral therapy

Serum hepcidin levels in women infected with HIV-1 under antiviral therapy

Iron autointoxication in a 16-year-old girl: a protective role for hepcidin?

Marginally excessive iron loading transiently blocks mucosal iron uptake in iron-deficient rats

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