title: Succinate ester derivative of δ-tocopherol enhances the protective effects against60Co γ-ray-induced hematopoietic injury through granulocyte colony-stimulating factor induction in mice.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zhong-Tang
authors.initials: ZT
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Yi
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Ren-Jun
authors.initials: RJ
authors.lastname: Peng
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zu-Yin
authors.initials: ZY
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Xiong
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Shan
authors.affiliation: Department of Medicinal Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Ri-Fang
authors.initials: RF
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Key Laboratory for Radiobiology (BKLRB), Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jun-Xing
authors.initials: JX
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cong
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003037:Cobalt Radioisotopes / Q000737:chemistry*; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D020714:Maximum Tolerated Dose; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003037:Cobalt Radioisotopes; D011837:Radiation-Protective Agents; D016179:Granulocyte Colony-Stimulating Factor; C000615395:Cobalt-60; D024502:alpha-Tocopherol