Nutritional hepatic iron overload is not prevented by parenteral hepcidin substitution therapy in mice.
The peptide hormone hepcidin functions as a negative regulator of intestinal Fe absorption and Fe recycling. Since its discovery as a systemic negative regulator of Fe metabolism, hepcidin has attracted enormous interest as a potential drug for the treatment and/or prevention of several forms of Fe overload. We therefore tested whether multiple doses of intraperitoneally administered synthetic renatured hepcidin can prevent hepatic Fe loading in mice concurrently fed an Fe-rich diet, and whether the same treatment affects hepatic Fe stores in mice fed a normal diet. Cohorts of male mice were fed either a normal defined diet (180 parts per million Fe) or an Fe-rich diet (the same diet supplemented with 2 % carbonyl iron for 2 weeks). Concurrently, half of the animals in each diet group received 100 μg of renatured hepcidin intraperitoneally every 12 h, for the same 2-week period. The second half of the animals received PBS only. The renatured synthetic hepcidin demonstrated biological activity by significantly decreasing transferrin saturation, which lasted for up to 24 h after a single hepcidin dose. However, the 14 d intraperitoneal hepcidin therapy did not prevent hepatic Fe overload in mice fed the Fe-rich diet, nor did it affect hepatic Fe stores in mice fed the normal diet. Both hepcidin agonists and antagonists are expected to have broad therapeutic potential. The absence of an effect of biologically active hepcidin on hepatic Fe loading shows the need for thorough future studies on the hepcidin regulation of Fe absorption and tissue distribution.
Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20              Prague 2, Czech Republic.
Tereza
T
Sillerova
Jan
J
Zivny
Daniel
D
Vyoral
Jiri
J
Petrak
D000821:Animal Feed; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004032:Diet; D064451:Hepcidins; D007274:Injections, Intraperitoneal; D019190:Iron Overload / Q000517:prevention & control*; D019266:Iron, Dietary / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D014168:Transferrin
D023181:Antimicrobial Cationic Peptides; C579599:Hamp protein, mouse; D064451:Hepcidins; D019266:Iron, Dietary; D014168:Transferrin