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JTZ-951 (enarodustat), a hypoxia-inducible factor prolyl hydroxylase inhibitor, improves iron utilization and anemia of inflammation: Comparative study against recombinant erythropoietin in rat
- Source :
- European journal of pharmacology. 898
- Publication Year :
- 2020
-
Abstract
- Anemia with inflammation-induced defective iron utilization is a pathological condition observed in patients suffering from chronic kidney disease (CKD) or chronic inflammatory disease. There is no reasonable treatment for these conditions, because the effects of erythropoiesis stimulating agents (ESAs) or iron supplementation in the treatment of anemia are insufficient. JTZ-951 (enarodustat) has been characterized as a novel, orally bioavailable inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), and has been developed as a novel therapeutic agent for anemia with CKD. In this study, the effects of JTZ-951 on iron utilization during erythropoiesis and on anemia of inflammation were compared with those of recombinant human erythropoietin (rHuEPO) using normal rat and rat model of anemia of inflammation. In normal rats, under conditions in which JTZ-951 and rHuEPO showed similar erythropoietic effect, repeated doses of JTZ-951 induced erythropoiesis while retaining the hemoglobin content in red blood cells, while administration of rHuEPO resulted in decrease in some erythrocyte-related parameters. As for iron-related parameters during erythropoiesis, JTZ-951 exhibited more efficient iron utilization compared to rHuEPO. A single dose of JTZ-951 resulted in decrease in hepcidin expression observed within 24 h after administration, but a single dose of rHuEPO did not. In a rat model of anemia of inflammation (also known as a model with functional iron-deficiency), JTZ-951 showed erythropoietic effect, in contrast with rHuEPO. These results suggest that, unlike rHuEPO, JTZ-951 stimulates erythropoiesis by increasing iron utilization, and improves anemia of inflammation.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Erythrocytes
Anemia
Pyridines
Iron
Inflammation
Hypoxia-Inducible Factor-Proline Dioxygenases
03 medical and health sciences
0302 clinical medicine
Hepcidins
Hepcidin
hemic and lymphatic diseases
Internal medicine
medicine
Animals
Erythropoiesis
Enzyme Inhibitors
Erythropoietin
Pharmacology
biology
Anemia, Iron-Deficiency
business.industry
Triazoles
medicine.disease
Arthritis, Experimental
Recombinant Proteins
030104 developmental biology
Endocrinology
Hypoxia-inducible factors
N-substituted Glycines
Rats, Inbred Lew
biology.protein
Hematinics
Female
Hemoglobin
medicine.symptom
business
030217 neurology & neurosurgery
Biomarkers
Kidney disease
medicine.drug
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 898
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....b5092e674af643288ad819bfcc32727a