ID | 113812 |
Author |
Hamano, Hirofumi
Tokushima University
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Niimura, Takahiro
Tokushima University
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Horinouchi, Yuya
Tokushima University
Takechi, Kenshi
Tokushima University
Goda, Mitsuhiro
Tokushima University
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Chuma, Masayuki
Tokushima University
Izawa-Ishizawa, Yuki
Tokushima University
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Fukushima, Keijo
Tokushima University
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Tsuchiya, Koichiro
Tokushima University
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Ishizawa, Keisuke
Tokushima University
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Tamaki, Toshiaki
Tokushima University|Anan Medical Center
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|
Keywords | Proton pump inhibitor
Hepcidin
Iron deficiency
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Content Type |
Journal Article
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Description | Proton pump inhibitors (PPIs) have been used worldwide to treat gastrointestinal disorders. A recent study showed that long-term use of PPIs caused iron deficiency; however, it is unclear whether PPIs affect iron metabolism directly. We investigated the effect of PPIs on the peptide hepcidin, an important iron regulatory hormone. First, we used the FDA Adverse Event Reporting System database and analyzed the influence of PPIs. We found that PPIs, as well as H2 blockers, increased the odds ratio of iron-deficient anemia. Next, HepG2 cells were used to examine the action of PPIs and H2 blockers on hepcidin. PPIs augmented hepcidin expression, while H2 blockers did not. In fact, the PPI omeprazole increased hepcidin secretion, and omeprazole-induced hepcidin upregulation was inhibited by gene silencing or the pharmacological inhibition of the aryl hydrocarbon receptor. In mouse experiments, omeprazole also increased hepatic hepcidin mRNA expression and blood hepcidin levels. In mice treated with omeprazole, protein levels of duodenal and splenic ferroportin decreased. Taken together, PPIs directly affect iron metabolism by suppressing iron absorption through the inhibition of duodenal ferroportin via hepcidin upregulation. These findings provide a new insight into the molecular mechanism of PPI-induced iron deficiency.
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Journal Title |
Toxicology Letters
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ISSN | 03784274
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NCID | AA00864457
AA1154013X
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Publisher | Elsevier
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Volume | 318
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Start Page | 86
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End Page | 91
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Published Date | 2019-10-24
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Rights | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Author
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departments |
Medical Sciences
University Hospital
Pharmaceutical Sciences
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