Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway.
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.
PMID: 28939421 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Han X, Zhang J, Xue X, Zhao Y, Lu L, Cui M, Miao W, Fan S Tags: Free Radic Biol Med Source Type: research