Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 113, Issue -, Pages 59-70Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2017.09.014
Keywords
Ionizing radiation; Theaflavin; Hematopoietic stem cells; Reactive oxygen species; Nuclear factor erythroid 2-related factor 2
Funding
- National Natural Science Foundation of China [81572969, 81402633, 81370598]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-017]
- Technology and Development and Research Projects for Research Institutes, Ministry of Science and Technology [2014EG150134]
- Natural Science Foundation of Tianjin [16JCQNJC13600]
- Youth Backbone Fund of IRM-CAMS [2017032]
- Tianjin Science & Technology Pillar Program [14ZCZDSY00001]
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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.
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