title: Hepcidin induction limits mobilisation of splenic iron in a mouse model of secondary iron overload.
abstract: Venesection has been proposed as a treatment for hepatic iron overload in a number of chronic liver disorders that are not primarily linked to mutations in iron metabolism genes. Our aim was to analyse the impact of venesection on iron mobilisation in a mouse model of secondary iron overload. C57Bl/6 mice were given oral iron supplementation with or without phlebotomy between day 0 (D0) and D22, and the results were compared to controls without iron overload. We studied serum and tissue iron parameters, mRNA levels of hepcidin1, ferroportin, and transferrin receptor 1, and protein levels of ferroportin in the liver and spleen. On D0, animals with iron overload displayed elevations in iron parameters and hepatic hepcidin1 mRNA. By D22, in the absence of phlebotomies, splenic iron had increased, but transferrin saturation had decreased. This was associated with high hepatic hepcidin1 mRNA, suggesting that iron bioavailability decreased due to splenic iron sequestration through ferroportin protein downregulation. After 22days with phlebotomy treatments, control mice displayed splenic iron mobilisation that compensated for the iron lost due to phlebotomy. In contrast, phlebotomy treatments in mice with iron overload caused anaemia due to inadequate iron mobilisation. In conclusion, our model of secondary iron overload led to decreased plasma iron associated with an increase in hepcidin expression and subsequent restriction of iron export from the spleen. Our data support the importance of managing hepcidin levels before starting venesection therapy in patients with secondary iron overload that are eligible for phlebotomy.
authors.affiliation: UMR INSERM U991, University of Rennes1, Rue Henri le Guilloux, 35033 Rennes, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Camberlein
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Abgueguen
authors.forename: Nadia
authors.initials: N
authors.lastname: Fatih
authors.forename: François
authors.initials: F
authors.lastname: Canonne-Hergaux
authors.forename: Patricia
authors.initials: P
authors.lastname: Leroyer
authors.forename: Bruno
authors.initials: B
authors.lastname: Turlin
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D064451:Hepcidins; D007501:Iron / Q000097:blood / Q000493:pharmacokinetics*; D019190:Iron Overload / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018962:Phlebotomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution; D000098742:Ferroportin
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D000098742:Ferroportin; D007501:Iron