Retinoic acid modulates iron metabolism imbalance in anemia of inflammation induced by LPS via reversely regulating hepcidin and ferroportin expression

Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):280-285. doi: 10.1016/j.bbrc.2018.11.022. Epub 2018 Nov 14.


The present study was designed to investigate the effect of retinoic acid (RA) on anemia of inflammation (AI) induced by lipopolysaccharide (LPS) and explore the potential mechanisms. BALB/c mice were randomly assigned into four groups: control group; LPS (10 mg/kg) group, LPS + RA (3 mg/kg) and LPS + RA (15 mg/kg) groups. Red blood cell count (RBC), hemoglobulin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin contentration (MCHC), erythropoietin (EPO) and iron content in both serum and liver tissue were measured. The AI model induced by LPS was successfully established represented by the decreases in RBC, Hb, HCT, MCV, MCHC and EPO for anemia indicators and by the increases in TNF-α, IL-18 and IL-1β contents for inflammation indicators. However, supplementation of RA increased the levels of anemia indicators and decreased the content of inflammation indicators. In addition, RA increased the content of iron in serum, while decreased its content in liver tissue. Furthermore, RA down-regulated the protein expression of hepcidin, toll-like receptor 4 (TLR4) and p-p65 in liver tissue, while up-regulated that of ferroportin. RA modulates iron metabolism imbalance in AI induced by LPS via reversely regulating hepcidin and ferroportin expression, which might be mediated by TLT-4/NFκB signaling pathway.

Keywords: Anemia indicators; Anemia of inflammation; Inflammation indicators; Lipopolysaccharide; Phosphorylated p-65; Retinoic acid; Toll-like receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / blood
  • Anemia / metabolism*
  • Anemia / pathology*
  • Animals
  • Cation Transport Proteins / metabolism*
  • Cytokines / blood
  • Down-Regulation / drug effects
  • Hepcidins / metabolism*
  • Inflammation / blood
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Iron / metabolism*
  • Lipopolysaccharides
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred BALB C
  • Phosphorylation / drug effects
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / metabolism
  • Tretinoin / pharmacology*


  • Cation Transport Proteins
  • Cytokines
  • Hepcidins
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • metal transporting protein 1
  • Tretinoin
  • Iron