Iron Supplementation in Suckling Piglets: How to Correct Iron Deficiency Anemia without Affecting Plasma Hepcidin Levels

Rafał R Starzyński,Paweł Lipiński,Michał Mickiewicz,Coby M M Laarakkers,Dorine W Swinkels,Harold Tjalsma,Agnieszka Styś,Marek Pieszka,James R Connor

doi:10.1371/journal.pone.0064022

Abstract

The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level.

Highlights

Iron deficiency is considered to be the most common mammalian nutritional deficiency [1] and is most prevalent in the neonatal period [2]
For decades pigs have been selected for large litter size, high birth weight and fast growth, which resulted in greater body blood volume, red blood cells (RBC) count, and in consequence, in increased iron demands
We have recently demonstrated that excessive loading of piglets with iron dextran induces hepcidin expression at the mRNA level in the liver, and may perturbate the utilization of iron released from this compound by blocking ferroportin [10], [20]

Summary

Introduction

Iron deficiency is considered to be the most common mammalian nutritional deficiency [1] and is most prevalent in the neonatal period [2]. For decades pigs have been selected for large litter size, high birth weight and fast growth, which resulted in greater body blood volume, red blood cells (RBC) count, and in consequence, in increased iron demands Both hepatic iron reserves and the sow’s milk are nowadays not sufficient to meet iron requirements in suckling piglets [3], [4], [7]. The blood flow iron is complexed with transferrin (Tf) and transported to the bone marrow to allow hemoglobin synthesis It seems that the optimal iron supplementation in piglets should meet two main criteria: 1) the delivery of sufficient amount of iron for erythropoiesis; 2) the avoidance of a dysfunctional increase in plasma hepcidin levels. We have developed a mass spectrometry assay to quantify bioactive hepcidin-25 in piglet plasma and assessed different protocols of piglet supplementation with iron dextran for their ability to stimulate recovery from neonatal IDA without inducing an unfavorable increase in plasma hepcidin

Materials and Methods

Results and Discussion

Author Contributions