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Regulators impeding erythropoiesis following iron supplementation in a clinically relevant rat model of iron deficiency anemia with inflammation

 Sung Yeon Ham  ;  Ji Hae Jun  ;  Hye-Bin Kim  ;  Jae-Kwang Shim  ;  Gisong Lee  ;  Young-Lan Kwak 
 LIFE SCIENCES, Vol.310 : 121124, 2022-12 
Journal Title
Issue Date
Anemia* ; Anemia, Iron-Deficiency* / drug therapy ; Animals ; Biomarkers ; Dietary Supplements ; Erythropoiesis ; Erythropoietin* / pharmacology ; Hemoglobins ; Hepcidins / metabolism ; Inflammation / complications ; Inflammation / drug therapy ; Iron / metabolism ; Iron Deficiencies* ; Male ; Rats ; Rats, Sprague-Dawley
Hepcidin ; Inflammation ; iron ; iron deficiency anemia
Aims: While elevated hepcidin levels with inflammation have been postulated as a putative mechanism hindering effective erythropoiesis after intravenous (IV) iron therapy in anemic patients undergoing surgery, little is known about the concomitant changes in other major regulators affecting erythropoiesis. This study investigated the activities of relevant regulators after iron replenishment in a rat model of iron deficiency anemia with inflammation.

Main methods: Inflammation was induced by administration of complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. After 2 weeks of CFA treatment, the rats received IV iron (CFA‑iron) or saline (CFA-saline). The control group received saline instead of CFA and iron (saline-saline). At 1, 3, and 10 days after iron or saline treatment, inflammatory cytokines, oxidative markers, iron profiles, hepcidin, erythropoietin (EPO), erythroferrone (ERFE), fibroblast growth factor 23 (FGF 23), and expression of mRNA and proteins in the liver involved in hepcidin signaling pathways were measured.

Key findings: CFA treatment and iron restriction decreased hemoglobin and serum iron levels, significantly increasing inflammatory and oxidative markers. Iron supplementation did not restore hemoglobin levels despite improved iron profiles. CFA injections increased hepcidin and FGF 23 levels and decreased EPO and ERFE levels, which further intensified after iron supplementation with concomitantly elevated levels of oxidative stress and inflammatory markers.

Significance: Under inflammatory conditions, IV iron administration exacerbated inflammatory and oxidative stress and did not resolve anemia, even under iron deficiency conditions. Iron therapy exerted adverse influences on the changes in key regulators toward impeding erythropoiesis that was already impeded by inflammation.
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Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
Shim, Jae Kwang(심재광) ORCID logo https://orcid.org/0000-0001-9093-9692
Jun, Ji Hae(전지혜) ORCID logo https://orcid.org/0000-0002-8080-0715
Ham, Sung Yeon(함성연) ORCID logo https://orcid.org/0000-0001-8619-4595
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