Succinate ester derivative of [delta]-tocopherol enhances the protective effects against 60Co [gamma]-ray-induced hematopoietic injury through granulocyte colony-stimulating factor induction in mice

α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has...

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Published in:Scientific reports 2017-02, Vol.7, p.40380
Main Authors: Li, Zhong-tang, Wang, Li-mei, Yi, Li-rong, Jia, Chao, Bai, Fan, Peng, Ren-jun, Yu, Zu-yin, Xiong, Guo-lin, Xing, Shuang, Shan, Ya-jun, Yang, Ri-fang, Dong, Jun-xing, Cong, Yu-wen
Format: Article
Language:English
Subjects:
Bone marrow
Colonies
Colony-stimulating factor
Granulocyte colony-stimulating factor
Granulocytes
Hematopoietic stem cells
Lethality
Leukocytes (granulocytic)
Pancytopenia
Post-irradiation
Progenitor cells
Radiation
Radiation protection
Radioprotective agents
Rodents
Toxicity
Vitamin E
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Summary:α-tocopherol succinate (α-TOS), γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have drawn large attention due to their efficacy as radioprotective agents. α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI). Because α-TOS has been shown to act superior to α-tocopherol (α-TOH) in mice by reducing lethality following total body irradiation (TBI), we hypothesized succinate may be contribute to the radioprotection of α-TOS. To study the contributions of succinate and to identify stronger radioprotective agents, we synthesized α-, γ- and δ-TOS. Then, we evaluated their radioprotective effects and researched further mechanism of δ-TOS on hematological recovery post-irradiation. Our results demonstrated that the chemical group of succinate enhanced the effects of α-, γ- and δ-TOS upon radioprotection and granulocyte colony-stimulating factor (G-CSF) induction, and found δ-TOS a higher radioprotective efficacy at a lower dosage. We further found that treatment with δ-TOS ameliorated radiation-induced pancytopenia, augmenting cellular recovery in bone marrow and the colony forming ability of bone marrow cells in sublethal irradiated mice, thus promoting hematopoietic stem and progenitor cell recovery following irradiation exposure. δ-TOS appears to be an attractive radiation countermeasure without known toxicity, but further exploratory efficacy studies are still required.
ISSN:2045-2322
DOI:10.1038/srep40380