Collectively, our data highlight a novel role of Prx2 in iron homeostasis. Prx2 is a key cytoprotector against IO that is induced either by iron supplementation or due to chronic hemolysis as in β-thalassemia. Prx2 is required to support STAT3 transcriptional activity and regulation of Hamp expression. Antioxid. Redox Signal. 28, 1-14.

We demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.

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renal insufficiency. Furthermore, the question raises if the TRP metabolism has a potential link to iron deficiency (ID) or iron deficiency anemia (IDA). This issue is not covered in the current literature. Aims: This prospective study aimed at evaluating the potential association between iron metabolism and hemoglobin (Hb) concentrations and the TRP metabolism in a large cohort of patients sub-grouped by the presence or absence ID or anemia. Methods: In this prospective study, 430 patients, who were admitted by general practitioners and specialists to the outpatient clinic of the Institute of Clinical Chemistry and Laboratory Medicine of the General Hospital Steyr (Steyr, Austria) for a medical check-up of their actual iron status, were included. All participants provided their written informed consent. They underwent venous blood sampling after an overnight fasting state in the morning (between 8.00 and 10.00 a.m.). The samples were used to investigate the iron metabolism (i.e., Hb, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], ferritin, transferrin saturation [TSAT], serum iron, transferrin, soluble transferrin receptor [sTfR], reticulocyte hemoglobin [CHr]), and also the TRP metabolism (TRP, kynurenine [KYN], kynurenic acid [KYNA], KYN/ TRP ratio, KYNA/KYN index). Serum concentrations of TRP, KYN, and KYNA were measured by high-pressure liquid-chromatography Results: Serum TRP, KYN and KYNA concentrations were positively correlated with Hb (p-values <0.001, 0.029, and <0.001) and ferritin (p-values 0.033, 0.008, and <0.001) measurements. In total, 159 patients with ID had significantly lower median (interquartile range) TRP (58.

Introduction: An insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as the key pathogenetic feature of HFE-related hereditary hemochromatosis (HH). There is a growing interest in measuring the hepcidin levels, which may improve diagnosis, prognostic evaluation and clinical management of HH. Nevertheless, few investigative tools are available: an immunodot method for urinary hepcidin developed by a single centre (UCLA), not yet ready for large-scale diffusion, and mass spectrometry (MS) based assays, such as surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF-MS). The latter is well suited to small peptides like hepcidin, and can rapidly analyze crude samples with high throughput. Until now, urinary hepcidin has been measured by SELDI-TOF-MS only in small groups of C282Y homozygous patients, the majority of them under phlebotomy treatment. No data are available on C282Y/H63D compound heterozygotes, that can develop a milder clinical form of HH. This study was aimed to measure urinary hepcidin levels by SELDI-TOF-MS in a large group of HH patients. Methods: We used a protocol based on PBSIIc mass spectromer and Normal Phase chips similar to that recently proven successful for semi-quantitative detection of urinary hepcidin. Urinary samples from 30 control subjects were compared to those obtained from 80 HH patients (57 C282Y homozygotes, 23 C282Y/H63D compound heterozygotes). Eighteen C282Y homozygotes and 11 C282Y/H63D compound heterozygotes were analyzed at diagnosis, the remainder during maintenance phlebotomy (at least 30 days from last phlebotomy). Results: C282Y homozygotes had significantly lower urinary hepcidin levels vs. controls either at diagnosis, or after phlebotomy (P &lt; 0.05). C282Y/H63D compound heterozygotes had hepcidin levels at diagnosis similar to controls, while the hepcidin:ferritin ratio was significantly decreased (P &lt; 0.001) suggesting a relatively inappropriate hepcidin production. Moreover, also in this group means hepcidin levels after phlebotomy were significantly lower than in controls (P &lt; 0.001). Samples from 12 randomly selected control subjects were sent to UCLA for duplicate measurement by the immunodot method, yielding a good correlation (r= 0.77; P&lt;0.0001). Conclusions: SELDI-TOF-MS assay is confirmed to be a potentially useful tool for measuring hepcidin levels in HH. The very low hepcidin levels observed in both genotypes after phlebotomy, may suggest that iron depletion as currently achieved by standard protocols may not be the best therapy from a pathophysiological standpoint.