PMID- 28939421
OWN - NLM
STAT- MEDLINE
DCOM- 20180910
LR  - 20220318
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 113
DP  - 2017 Dec
TI  - Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the 
      NRF2 pathway.
PG  - 59-70
LID - S0891-5849(17)30758-X [pii]
LID - 10.1016/j.freeradbiomed.2017.09.014 [doi]
AB  - It has been well established that reactive oxygen species (ROS) play a critical 
      role in ionizing radiation (IR)-induced hematopoietic injury. Theaflavin (TF), a 
      polyphenolic compound from black tea, has been implicated in the regulation of 
      endogenous cellular antioxidant systems. However, it remains unclear whether TF 
      could ameliorate IR-induced hematopoietic injury, particularly the hematopoietic 
      stem cell (HSC) injury. In this study, we explored the potential role of TF in 
      IR-induced HSC injury and the underlying mechanism in a total body irradiation 
      (TBI) mouse model. Our results showed that TF improved survival of irradiated 
      wild-type mice and ameliorated TBI-induced hematopoietic injury by attenuating 
      myelosuppression and myeloid skewing, increasing HSC frequency, and promoting 
      reconstitution of irradiated HSCs. Furthermore, TF inhibited TBI-induced HSC 
      senescence. These effects of TF were associated with a decline in ROS levels and 
      DNA damage in irradiated HSCs. TF reduced oxidative stress mainly by 
      up-regulating nuclear factor erythroid 2-related factor 2 (NRF2) and its 
      downstream targets in irradiated Lineage(-)c-kit(+) positive cells. However, TF 
      failed to improve the survival, to increase HSC frequency and to reduce ROS 
      levels of HSCs in irradiated Nrf2(-/-) mice. These findings suggest that TF 
      ameliorates IR-induced HSC injury via the NRF2 pathway. Therefore, TF has the 
      potential to be used as a radioprotective agent to ameliorate IR-induced 
      hematopoietic injury.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Han, Xiaodan
AU  - Han X
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China. Electronic address: 
      hanxiaodan1202@163.com.
FAU - Zhang, Junling
AU  - Zhang J
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China. Electronic address: 
      zhangjunling@irm-cams.ac.cn.
FAU - Xue, Xiaolei
AU  - Xue X
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China.
FAU - Zhao, Yu
AU  - Zhao Y
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China.
FAU - Lu, Lu
AU  - Lu L
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China.
FAU - Cui, Ming
AU  - Cui M
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China.
FAU - Miao, Weimin
AU  - Miao W
AD  - State Key Laboratory of Experimental Hematology, Institute of Hematology and 
      Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Tianjin 300041,China.
FAU - Fan, Saijun
AU  - Fan S
AD  - Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, 
      Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy 
      of Medical Science, Tianjin 300192, China. Electronic address: 
      fansaijun@irm-cams.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170920
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Biflavonoids)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Radiation-Protective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 1IA46M0D13 (theaflavin)
RN  - 8R1V1STN48 (Catechin)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Biflavonoids/*pharmacology/therapeutic use
MH  - Catechin/*pharmacology/therapeutic use
MH  - DNA/radiation effects
MH  - *DNA Damage
MH  - Hematopoietic Stem Cells/*drug effects/radiation effects
MH  - Male
MH  - Mice
MH  - NF-E2-Related Factor 2/*drug effects/metabolism
MH  - Oxidative Stress/drug effects
MH  - Radiation Injuries, Experimental/*prevention & control
MH  - *Radiation, Ionizing
MH  - Radiation-Protective Agents/pharmacology
MH  - Reactive Oxygen Species
MH  - *Signal Transduction
MH  - Whole-Body Irradiation
OTO - NOTNLM
OT  - Hematopoietic stem cells
OT  - Ionizing radiation
OT  - Nuclear factor erythroid 2-related factor 2
OT  - Reactive oxygen species
OT  - Theaflavin
EDAT- 2017/09/25 06:00
MHDA- 2018/09/11 06:00
CRDT- 2017/09/24 06:00
PHST- 2017/07/20 00:00 [received]
PHST- 2017/09/08 00:00 [revised]
PHST- 2017/09/17 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2018/09/11 06:00 [medline]
PHST- 2017/09/24 06:00 [entrez]
AID - S0891-5849(17)30758-X [pii]
AID - 10.1016/j.freeradbiomed.2017.09.014 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2017 Dec;113:59-70. doi: 
      10.1016/j.freeradbiomed.2017.09.014. Epub 2017 Sep 20.