PMID- 30334352
OWN - NLM
STAT- MEDLINE
DCOM- 20200611
LR  - 20220111
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 1
DP  - 2019 Jan
TI  - Radioprotective effects of roxadustat (FG-4592) in haematopoietic system.
PG  - 349-356
LID - 10.1111/jcmm.13937 [doi]
AB  - BACKGROUND: Ionizing radiation often causes severe injuries to radiosensitive 
      tissues, especially haematopoietic system. Novel radioprotective drugs with low 
      toxicity and high effectiveness are required. Prolyl hydroxylases domain (PHD) 
      inhibitors have been reported to protect against radiation-induced 
      gastrointestinal toxicity. In this study, we demonstrated the protective effects 
      of a PHD inhibitor, roxadustat (FG-4592), against radiation-induced 
      haematopoietic injuries in vitro and in vivo. METHODS: Tissue injuries were 
      evaluated by Haematoxilin-Eosin (HE) staining assay. HSCs were determined by flow 
      cytometry with the Lin(-) Sca-1(+) c-Kit(+) (LSK) phenotype. Cell apoptosis was 
      determined by Annexin V/PI staining assay. Immunofluorescence was performed to 
      measure radiation-induced DNA damage. A western blot assay was used to detect the 
      changes of proteins related to apoptosis. RESULTS: We found that FG-4592 
      pretreatment increased survival rate of irradiated mice and protected bone marrow 
      and spleen from damages. Number of bone marrow cells (BMCs) and LSK cells were 
      also increased both in irradiated mice and recipients after bone marrow 
      transplantation (BMT). FG-4592 also protected cells against radiation-induced 
      apoptosis and double strand break of DNA. CONCLUSIONS: Our data showed that 
      FG-4592 exhibited radioprotective properties in haematopoietic system both 
      in vivo and in vitro through up-regulating HIF-1alpha, indicating a potential role of 
      FG-4592 as a novel radioprotector.
CI  - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Zhang, Pei
AU  - Zhang P
AUID- ORCID: 0000-0002-3297-899X
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
AD  - Department of Radiation Oncology, Chinese PLA General Hospital, Beijing, China.
FAU - Du, Jicong
AU  - Du J
AUID- ORCID: 0000-0002-2088-4603
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Zhao, Hainan
AU  - Zhao H
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Cheng, Ying
AU  - Cheng Y
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Dong, Suhe
AU  - Dong S
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Yang, Yanyong
AU  - Yang Y
AUID- ORCID: 0000-0002-6882-5274
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Li, Bailong
AU  - Li B
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Gao, Fu
AU  - Gao F
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Sun, Xuejun
AU  - Sun X
AD  - Department of Navy Aviation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Cai, Jianming
AU  - Cai J
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
FAU - Liu, Cong
AU  - Liu C
AD  - Department of Radiation Medicine, Faculty of Naval Medicine, Second Military 
      Medical University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181018
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Isoquinolines)
RN  - 0 (Radiation-Protective Agents)
RN  - TE7660XO1C (Glycine)
RN  - X3O30D9YMX (roxadustat)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/radiation effects
MH  - Bone Marrow Cells/drug effects/radiation effects
MH  - Bone Marrow Transplantation
MH  - DNA Damage
MH  - Glycine/*analogs & derivatives/pharmacology
MH  - Hematopoiesis/*drug effects
MH  - Hematopoietic Stem Cells/*drug effects/radiation effects
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Isoquinolines/*pharmacology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Radiation Injuries/*prevention & control
MH  - Radiation-Protective Agents/*pharmacology
MH  - Spleen/drug effects/radiation effects
MH  - Survival Rate
MH  - Whole-Body Irradiation/mortality
PMC - PMC6307774
OTO - NOTNLM
OT  - HIF
OT  - FG-4592
OT  - irradiation
OT  - radioprotection
EDAT- 2018/10/20 06:00
MHDA- 2020/06/12 06:00
PMCR- 2019/01/01
CRDT- 2018/10/19 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2018/09/03 00:00 [accepted]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2020/06/12 06:00 [medline]
PHST- 2018/10/19 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - JCMM13937 [pii]
AID - 10.1111/jcmm.13937 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 Jan;23(1):349-356. doi: 10.1111/jcmm.13937. Epub 2018 Oct 
      18.