Urinary Hepcidin Levels in Iron-Deficient and Iron-Supplemented Piglets Correlate with Hepcidin Hepatic mRNA and Serum Levels and with Body Iron Status

Abstract

Among livestock, domestic pig (Sus scrofa) is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS) are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status.

Long-term Effect of Split Iron Dextran/Hemoglobin Supplementation on Erythrocyte and Iron Status, Growth Performance, Carcass Parameters, and Meat Quality of Polish Large White and 990 Line Pigs

“…However, routinely applied dose of 200 mg Fe per piglet in the form of a single intramuscular injection of FeDex seems not being efficiently metabolized and detoxified [8]. Moreover, we have previously reported that high iron parenteral supplementation with FeDex induces expression of hepcidin (Hepc) [8,12,13], a 25-amino acid peptide hormone, the master regulator of the systemic iron homeostasis in vertebrates [14]. It is well established that high Hepc may perturb body iron homeostasis by inhibiting both duodenal iron absorption and iron recycling by macrophages of the reticuloendothelial system (RES) that catabolize heme contained in phagocytosed senescent RBC [15].…”

“…To minimize both toxicity of supplemental iron and its capacity to induce hepcidin synthesis, we proposed several modifications of routine procedure of FeDex administration to piglets [8,12]. Furthermore, considering that heme preparations have been successfully used to prevent and treat IDA in humans [16][17][18], dogs [19], and pigs [20,21], we used bovine hemoglobin as heme iron supplement.…”

Iron Supplementation in Suckling Piglets: an Ostensibly Easy Therapy of Neonatal Iron Deficiency Anemia

“…In humans, the incidence of such risk has been clearly demonstrated in iron-supplemented women showing significantly decreased fractional iron absorption, which was associated with acute increase in hepcidin [57]. In our studies we have performed for the first time a comprehensive analysis of hepcidin expression (we measured the abundance of hepcidin mRNA in the liver as well as hepcidin concentration in blood plasma and urine) in suckling piglets supplemented with FeDex and in anemic, nonsupplemented animals [16,17,58]. Administration of large amounts of iron to piglets resulted in a significant increase in hepcidin expression, which appears immediately (only one day) after the injection of FeDex and is sustained at high level up to weaning (day 28 after birth).…”

“…Nevertheless, there is a general consensus regarding hemoglobin concentration to set the cutoff level of anemia in suckling piglets at 8g/dL [12,13] although some authors claim about higher values reaching 11-13 g/dL [14]. It is clear from many studies [15][16][17][18][19][20] including our own [15][16][17] that such level of Hgb is reachable only in piglets supplemented with very high doses of iron. Without iron supplementation IDA in piglets appears few days after birth.…”

“…It is important to underline that most iron supplementation therapies start on day 2 or 3 after birth, therefore, this initial, sensu stricto normal Hgb value is a convenient starting point for testing the efficacy of new supplementation procedures in both veterinary practice and research. On day 3, Hgb concentration in non-supplemented piglets drops to the level of 6-7 g/dL and at weaning is drastically decreased even up to 4-5 g/dL, which indicates a state of extreme anemia [15,16,21]. Due to the efficient supplementation widely used in suckling piglets (see chapter below), anemia was practically eliminated from pig husbandry, however, in research, anemic piglets still constitute an indispensable reference group for exploring molecular background of systemic iron metabolism in neonatal and early postnatal period.…”