Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of () following RBC transfusion in dogs with atraumatic hemorrhage.

Investigating the Molecular Mechanisms of Renal Hepcidin Induction and Protection upon Hemoglobin-Induced Acute Kidney Injury.

Hemolysis is known to cause acute kidney injury (AKI). The iron regulatory hormone hepcidin, produced by renal distal tubules, is suggested to exert a renoprotective role during this pathology. We aimed to elucidate the molecular mechanisms of renal hepcidin synthesis and its protection against hemoglobin-induced AKI.

Kidney tubule iron loading in experimental focal segmental glomerulosclerosis.

Kidney iron deposition may play a role in the progression of tubulointerstitial injury during chronic kidney disease. Here, we studied the molecular mechanisms of kidney iron loading in experimental focal segmental glomerulosclerosis (FSGS) and investigated the effect of iron-reducing interventions on disease progression. Thy-1.

Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone.

Erythroferrone (ERFE), the erythroid regulator of iron metabolism, inhibits hepcidin to increase iron availability for erythropoiesis. ERFE plays a pathological role during ineffective erythropoiesis as occurs in X-linked sideroblastic anemia (XLSA) and β-thalassemia. Its measurement might serve as an indicator of severity for these diseases.

Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium.

The liver hormone hepcidin regulates systemic iron homeostasis. Hepcidin is also expressed by the kidney, but exclusively in distal nephron segments. Several studies suggest hepcidin protects against kidney damage involving Fe overload.

Sustained Exposure to High Carbohydrate Availability Does Not Influence Iron-Regulatory Responses in Elite Endurance Athletes.

This study implemented a 2-week high carbohydrate (CHO) diet intended to maximize CHO oxidation rates and examined the iron-regulatory response to a 26-km race walking effort. Twenty international-level, male race walkers were assigned to either a novel high CHO diet (MAX = 10 g/kg body mass CHO daily) inclusive of gut-training strategies, or a moderate CHO control diet (CON = 6 g/kg body mass CHO daily) for a 2-week training period. The athletes completed a 26-km race walking test protocol before and after the dietary intervention.

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes.

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID.

Influence of Periodizing Dietary Carbohydrate on Iron Regulation and Immune Function in Elite Triathletes.

Sleeping with low carbohydrate (CHO) availability is a dietary strategy that may enhance training adaptation. However, the impact on an athlete's health is unclear. This study quantified the effect of a short-term "sleep-low" dietary intervention on markers of iron regulation and immune function in athletes.

The multifaceted role of iron in renal health and disease.

Iron is an essential element that is indispensable for life. The delicate physiological body iron balance is maintained by both systemic and cellular regulatory mechanisms. The iron-regulatory hormone hepcidin assures maintenance of adequate systemic iron levels and is regulated by circulating and stored iron levels, inflammation and erythropoiesis.

First-in-human Phase I studies of PRS-080#22, a hepcidin antagonist, in healthy volunteers and patients with chronic kidney disease undergoing hemodialysis.

In chronic kidney disease both renal insufficiency and chronic inflammation trigger elevated hepcidin levels, which impairs iron uptake, availability. and erythropoiesis. Here we report the two first-in-human phase 1 trials of PRS-080#22, a novel, rationally engineered Anticalin protein that targets and antagonizes hepcidin.

Acute carbohydrate ingestion does not influence the post-exercise iron-regulatory response in elite keto-adapted race walkers.

Objectives: Adhering to a low carbohydrate (CHO) high fat (LCHF) diet can alter markers of iron metabolism in endurance athletes. This investigation examined the re-introduction of CHO prior to, and during exercise on the iron-regulatory response to exercise in a homogenous (in regard to serum ferritin concentration) group of athletes adapted to a LCHF diet.

Design: Parallel groups design.

Provisional standardization of hepcidin assays: creating a traceability chain with a primary reference material, candidate reference method and a commutable secondary reference material.

Background Hepcidin concentrations measured by various methods differ considerably, complicating interpretation. Here, a previously identified plasma-based candidate secondary reference material (csRM) was modified into a serum-based two-leveled sRM. We validated its functionality to increase the equivalence between methods for international standardization.

Publisher Correction: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Endogenous hepcidin synthesis protects the distal nephron against hemin and hemoglobin mediated necroptosis.

Hemoglobinuria is associated with kidney injury in various hemolytic pathologies. Currently, there is no treatment available and its pathophysiology is not completely understood. Here we studied the potential detrimental effects of hemoglobin (Hb) exposure to the distal nephron (DN).

Sustained plasma hepcidin suppression and iron elevation by Anticalin-derived hepcidin antagonist in cynomolgus monkey.

Background And Purpose: Anaemia of chronic disease (ACD) has been linked to iron-restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here, we report the engineering of the human lipocalin-derived, small protein-based anticalin PRS-080 hepcidin antagonist with high affinity and selectivity.

Experimental Approach: Anticalin- and hepcidin-specific pharmacokinetic (PK)/pharmacodynamic modelling (PD) was used to design and select the suitable drug candidate based on t extension and duration of hepcidin suppression.

Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption.

Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption.

Cardiac Hepcidin Expression Associates with Injury Independent of Iron.

Background: Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD).

Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin-Mediated Kidney Injury.

Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma.

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

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.

Application of urine proteomics for biomarker discovery in drug-induced liver injury.

Abstract The leading cause of hepatic damage is drug-induced liver injury (DILI), for which currently no adequate predictive biomarkers are available. Moreover, for most drugs related to DILI, the mechanisms underlying the adverse reaction have not yet been elucidated. Urinary protein biomarker candidates for DILI have emerged in the past few years and correlate well with clinical studies for serum DILI biomarkers.

Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury.

Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker identification, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PCLS were incubated with acetaminophen (APAP), 3-acetamidophenol, diclofenac and lipopolysaccharide for 24-48 h.

Biomarkers for methotrexate-induced liver injury: urinary protein profiling of psoriasis patients.

Hepatic fibrosis is an adverse drug reaction of methotrexate (MTX) seen after long-term use in psoriasis patients. Currently, patients are monitored for MTX-induced hepatic fibrosis by performing liver biopsy, which is risky and burdensome for the patient, or by measuring plasma procollagen type III aminopeptide (PIIINP), which is not conclusive. The objective of this study was to identify novel predictive and preferably non-invasive biomarkers to monitor psoriasis patients for MTX-induced hepatic fibrosis.