PMID- 30458168
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20191210
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 843
DP  - 2019 Jan 15
TI  - Pharmacological inhibition of prolyl hydroxylase protects against 
      inflammation-induced anemia via efficient erythropoiesis and hepcidin 
      downregulation.
PG  - 113-120
LID - S0014-2999(18)30678-2 [pii]
LID - 10.1016/j.ejphar.2018.11.023 [doi]
AB  - 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 hydroxylase inhibitor desidustat was assessed as 
      an effective treatment of anemia of inflammation. In BALB/c mice, a single dose 
      treatment of desidustat attenuated the effect of lipopolysaccharide (LPS) - or 
      turpentine oil-induced inflammation and increased serum erythropoietin (EPO), 
      iron, and reticulocyte count, and decreased serum hepcidin levels. In turpentine 
      oil-induced anemia in BALB/c mice, repeated dose desidustat treatment increased 
      hemoglobin, RBC and hematocrit in a dose related manner. In female Lewis rats, 
      treatment with desidustat markedly reduced PGPS-induced anemia and increased 
      hemoglobin, red blood cell (RBC) and white blood cell (WBC) count, hematocrit, 
      serum iron and spleen iron. These effects of desidustat were associated with 
      reduction in hepcidin (HAMP) expression as well as reduction in serum hepcidin, 
      and increased EPO expression in liver and kidneys. Desidustat treatment caused a 
      significant increase in expression of Duodenal cytochrome B (DcytB), ferroportin 
      (FPN1) and divalent metal transporter 1 (DMT1) in duodenum, and FPN1 and monocyte 
      chemoattractant protein-1 (MCP-1) in liver suggesting an overall influence on 
      iron metabolism. Thus, pharmacological inhibition of prolyl hydroxylase enzymes 
      can be useful in treatment of anemia of inflammation.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Jain, Mukul
AU  - Jain M
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India. Electronic address: mukul.jain@zyduscadila.com.
FAU - Joharapurkar, Amit
AU  - Joharapurkar A
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Patel, Vishal
AU  - Patel V
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Kshirsagar, Samadhan
AU  - Kshirsagar S
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Sutariya, Brijesh
AU  - Sutariya B
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Patel, Maulik
AU  - Patel M
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Patel, Hiren
AU  - Patel H
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
FAU - Patel, Pankaj R
AU  - Patel PR
AD  - Zydus Research Centre, Cadila Healthcare Limited, Sarkhej Bavla NH 8 A, Moraiya, 
      Ahmedabad 382210, India.
LA  - eng
PT  - Journal Article
DEP - 20181117
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Hepcidins)
RN  - 0 (Prolyl-Hydroxylase Inhibitors)
RN  - 0 (Quinolones)
RN  - 11096-26-7 (Erythropoietin)
RN  - E1UOL152H7 (Iron)
RN  - Y962PQA4KS (desidustat)
SB  - IM
MH  - Anemia/*drug therapy/etiology/metabolism
MH  - Animals
MH  - Down-Regulation
MH  - Erythropoiesis/*drug effects
MH  - Erythropoietin/blood
MH  - Female
MH  - Hepcidins/blood/genetics
MH  - Inflammation/complications
MH  - Iron/metabolism
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Prolyl-Hydroxylase Inhibitors/pharmacology/*therapeutic use
MH  - Quinolones/pharmacology/*therapeutic use
MH  - Rats, Inbred Lew
MH  - Reticulocyte Count
OTO - NOTNLM
OT  - Anemia of inflammation
OT  - Desidustat
OT  - Hepcidin
OT  - Iron
EDAT- 2018/11/21 06:00
MHDA- 2019/04/16 06:00
CRDT- 2018/11/21 06:00
PHST- 2018/09/20 00:00 [received]
PHST- 2018/11/12 00:00 [revised]
PHST- 2018/11/16 00:00 [accepted]
PHST- 2018/11/21 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/11/21 06:00 [entrez]
AID - S0014-2999(18)30678-2 [pii]
AID - 10.1016/j.ejphar.2018.11.023 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Jan 15;843:113-120. doi: 10.1016/j.ejphar.2018.11.023. Epub 
      2018 Nov 17.