Pharmacological inhibition of prolyl hydroxylase protects against inflammation‐induced anemia via efficient erythropoiesis and hepcidin downregulation

  title={Pharmacological inhibition of prolyl hydroxylase protects against inflammation‐induced anemia via efficient erythropoiesis and hepcidin downregulation},
  author={M. Jain and A. Joharapurkar and V. Patel and S. Kshirsagar and B. Sutariya and Maulik S Patel and Hiren M Patel and P. Patel},
  journal={European Journal of Pharmacology},
ABSTRACT Chronic inflammatory diseases are often associated with anemia. In such conditions, anemia is generally treated with erythropoiesis stimulating agents (ESAs) which are associated with potentially hazardous side effects and poor outcomes. Suboptimal erythropoiesis in chronic inflammation is believed to be caused by elevated hepcidin levels, which causes blockade of iron in tissue stores. In the current work using rodent models of inflammation, an orally available small molecule prolyl… Expand
7 Citations
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Black pepper prevents anemia of inflammation by inhibiting hepcidin over-expression through BMP6-SMAD1/ IL6-STAT3 signaling pathway.
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HIF Prolyl Hydroxylase Inhibitors for COVID-19 Treatment: Pros and Cons
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Hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience.
Current clinical experience with HIF-PHIs is surveyed, potential therapeutic advantages are discussed, and safety concerns regarding long-term administration in patients with renal anemia are deliberate over. Expand
Iron Therapy in Chronic Kidney Disease: Days of Future Past
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Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.
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Hypoxia-Inducible Factor A ACKD ctivators in Renal Anemia : Current Clinical Experience
From the Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Department of Medical Cell Biology, Uppsala Universitet, Uppsala, Sweden; and Department of Molecular PhysiologyExpand


Hepcidin‐dependent and hepcidin‐independent regulation of erythropoiesis in a mouse model of anemia of chronic inflammation
Differences in erythrocyte parameters suggest anemia in many inflammatory states may not be fully explained by hepcidin‐mediated iron sequestration, and chronic anemia associated with inflammation may benefit from interventions protecting ery Throcyte number in addition to anti‐hePCidin interventions aimed at enhancing iron availability. Expand
Novel erythropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model.
Darbepoetin alfa treatment reversed ACD in this rodent model by increasing RBC production and RBC hemoglobinization while reducing siderosis and hypoferremia. Expand
Hepcidin regulation in the anemia of inflammation
Recent studies confirm an important role for the hepcidin–ferroportin axis in the development of anemia of inflammation, but also highlight the diverse and complex pathogenesis of this disorder depending on the underlying disease. Expand
Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia.
The efficacy of ZYAN1 in disease models of different etiologies suggests that it will be useful in treating wide spectrum of anemia patients and hematinic potential by combined effects on EPO release and efficient iron utilization is demonstrated. Expand
Erythropoietin's inhibiting impact on hepcidin expression occurs indirectly.
It is suggested that the role of Epo is to stimulate the synthesis of the erythroid regulator ERFE in erythroblasts, which ultimately downregulates hepcidin. Expand
Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases.
The role of PHD inhibitors in the treatment of anemia associated with chronic diseases is discussed and many orally active PHD inhibitor like roxadUSTat, molidustat, vadadustats, and desidustat are in late phase clinical trials. Expand
Iron regulation and erythropoiesis
  • E. Nemeth
  • Biology, Medicine
  • Current opinion in hematology
  • 2008
Regulation of hepcidin and iron availability for erythropoiesis has revealed unexpected pathways and much complexity and the renaissance of the study of iron regulation continues to reward researchers with interesting biology and potential therapeutic targets. Expand
Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis.
In vivo evidence is provided that Hamp1 suppression by the HIF pathway occurs indirectly through stimulation of EPO-induced erythropoiesis, the molecular basis of hypoxia/HIF-mediated hepcidin suppression in the liver remains unclear. Expand
The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation.
Modifications of hepcidin gene expression suggest a key role for hepciridin in iron homeostasis under various pathophysiological conditions, which may support the pharmaceutical use of hePCidin agonists and antagonists in various ironHomeostasis disorders. Expand
Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD.
The data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production and indicate that deranged oxygen sensing--not a loss of EPOProduction capacity--causes renal anemia. Expand