| アブストラクト | 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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| ジャーナル名 | Toxicology letters |
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| Pubmed追加日 | 2019/11/2 |
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| 投稿者 | Hamano, Hirofumi; Niimura, Takahiro; Horinouchi, Yuya; Zamami, Yoshito; Takechi, Kenshi; Goda, Mitsuhiro; Imanishi, Masaki; Chuma, Masayuki; Izawa-Ishizawa, Yuki; Miyamoto, Licht; Fukushima, Keijo; Fujino, Hiromichi; Tsuchiya, Koichiro; Ishizawa, Keisuke; Tamaki, Toshiaki; Ikeda, Yasumasa |
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| 組織名 | Department of Clinical Pharmacy, Institute of Biomedical Sciences, Tokushima;University Graduate School, Tokushima, Japan; Department of Pharmacy, Tokushima;University Hospital, Tokushima, Japan.;University Graduate School, Tokushima, Japan.;Department of Pharmacology, Institute of Biomedical Sciences, Tokushima;Clinical Trial Center for Developmental Therapeutics, Tokushima University;Hospital, Tokushima, Japan.;Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.;AWA Support Center, Tokushima University, Japan.;Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima;Department of Molecular Pharmacology, Institute of Biomedical Sciences, Tokushima;University Graduate School, Tokushima, Japan; Anan Medical Center, Tokushima,;Japan.;University Graduate School, Tokushima, Japan. Electronic address:;yasuike@tokushima-u.ac.jp. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/31669099/ |
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