Iron retention and distribution in the cadmium-induced iron deficiency

Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution strategies. Deeper insights into the pathophysiology of AI has led to the development of new therapeutics targeting inflammatory cytokines and the introduction of new iron formulations. Moreover, the discovery that the hormone, hepcidin, plays a key regulatory role in AI has stimulated the development of several therapeutic approaches targeting the function of this peptide. Hence, inflammation-driven hepcidin elevation causes iron retention in cells and tissues. Besides pathophysiological concepts and diagnostic approaches for AI, this review discusses current guidelines for iron replacement therapies with special emphasis on benefits, limitations, and unresolved questions concerning oral versus parenteral iron supplementation in chronic inflammatory diseases. Furthermore, the review explores how therapies aiming at curing the disease underlying AI can also affect anemia and discusses emerging hepcidin antagonizing drugs, which are currently under preclinical or clinical investigation.

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Iron Retention in Root Hemicelluloses Causes Genotypic Variability in the Tolerance to Iron Deficiency-Induced Chlorosis in Maize

Frontiers in Plant Science ◽

10.3389/fpls.2018.00557 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 8

Author(s):

Rongli Shi ◽

Michael Melzer ◽

Shaojian Zheng ◽

Andreas Benke ◽

Benjamin Stich ◽

...

Keyword(s):

Iron Deficiency ◽

Genotypic Variability ◽

Iron Retention

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Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications

Blood ◽

10.1182/blood-2008-12-195651 ◽

2009 ◽

Vol 113 (21) ◽

pp. 5277-5286 ◽

Cited By ~ 240

Author(s):

Igor Theurl ◽

Elmar Aigner ◽

Milan Theurl ◽

Manfred Nairz ◽

Markus Seifert ◽

...

Keyword(s):

Chronic Disease ◽

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Homeostasis ◽

Chronic Arthritis ◽

Deficiency Anemia ◽

Anemia Of Chronic Disease ◽

Regulatory Pathways ◽

Therapeutic Implications ◽

Iron Retention

Abstract The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux on binding to the iron export protein ferroportin. Many patients, however, present with both ACD and iron deficiency anemia (ACD/IDA), the latter resulting from chronic blood loss. We used a rat model of ACD resulting from chronic arthritis and mimicked ACD/IDA by additional phlebotomy to define differing iron-regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans with ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals with ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA persons, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients.

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DMT1 and FPN1 expression during infancy: developmental regulation of iron absorption

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00107.2003 ◽

2003 ◽

Vol 285 (6) ◽

pp. G1153-G1161 ◽

Cited By ~ 41

Author(s):

Weng-In Leong ◽

Christopher L. Bowlus ◽

Jonas Tallkvist ◽

Bo Lönnerdal

Keyword(s):

Iron Deficiency ◽

Iron Uptake ◽

Iron Absorption ◽

Developmental Regulation ◽

Total Iron ◽

Receptor Expression ◽

Body Iron ◽

Rat Pups ◽

Iron Deficient ◽

Iron Retention

Two iron transporters, divalent metal transporter1 (DMT1) and ferroportin1 (FPN1) have been identified; however, their role during infancy is unknown. We investigated DMT1, FPN1, ferritin, and transferrin receptor expression, iron absorption and tissue iron in iron-deficient rat pups, iron-deficient rat pups given iron supplements, and controls during early ( day 10) and late infancy ( day 20). With iron deficiency, DMT1 was unchanged and FPN1 was decreased (-80%) at day 10. Body iron uptake, mucosal iron retention, and total iron absorption were unchanged. At day 20, DMT1 increased fourfold and FPN1 increased eightfold in the low-Fe group compared with controls. Body iron uptake and total iron absorption were increased, and mucosal iron retention was decreased with iron deficiency. Iron supplementation normalized expression levels of the transporters, body iron uptake, mucosal iron retention, and total iron absorption of the low-Fe group to those of controls at day 20. In summary, the molecular mechanisms regulating iron absorption during early infancy differ from late infancy when they are similar to adult animals, indicating developmental regulation of iron absorption.

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