Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway

Publication date: December 2017
Source:Free Radical Biology and Medicine, Volume 113
Author(s): Xiaodan Han, Junling Zhang, Xiaolei Xue, Yu Zhao, Lu Lu, Ming Cui, Weimin Miao, Saijun Fan
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.

Graphical abstract

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