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Author:

Wang, Shaozheng (Wang, Shaozheng.) | Zuo, Zongchao (Zuo, Zongchao.) | Ouyang, Zhangyi (Ouyang, Zhangyi.) | Liu, Xinyu (Liu, Xinyu.) | Wang, Junke (Wang, Junke.) | Shan, Yajun (Shan, Yajun.) | Meng, Ruoxi (Meng, Ruoxi.) | Zhao, Zhenhu (Zhao, Zhenhu.) | Liu, Xiaolan (Liu, Xiaolan.) | Liu, Xiaoyan (Liu, Xiaoyan.) | Jin, Yiguang (Jin, Yiguang.) | Li, Zhongtang (Li, Zhongtang.) | Zhang, Hong (Zhang, Hong.) | Wang, Limei (Wang, Limei.) | Cong, Yuwen (Cong, Yuwen.)

Indexed by:

Scopus SCIE

Abstract:

To date only four recombinant growth factors, including Filgrastim (rhG-CSF), have been approved by FDA as radiomitigators to ameliorate hematopoietic acute radiation syndrome (H-ARS). These approved agents are not stable under room-temperature, needing to be stored at 2-8 degree celsius, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (delta-T3H), the most potent G-CSF-inducing agent among vitamin E isoforms, exhibited efficiency and selectivity on G-CSF production in comparison with TLR and STING agonists in mice. Five-dose delta-T3H was utilized as the optimal therapeutic regimen due to long-term G-CSF production and the best peripheral blood (PB) recovery of irradiated mice. Comparable with rhG-CSF, sequential administration of delta-T3H post-irradiation improved hematologic recovery and accelerated the regeneration of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow (BM) and spleen of 6.5Gy irradiated mice; and consistently enhanced repopulation of BMHSCs. In 4.0Gy irradiated nonhuman primates, delta-T3H exhibited comparable efficacy as rhG-CSF to promote PB recovery and colony-formation of BM-HPCs. Altogether, we demonstrated that sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production, indicated delta-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

Keyword:

Delta-tocotrienol Granulocyte colony -stimulating factor Radiation Radiomitigator Nonhuman primates Hematopoietic acute radiation syndrome

Author Community:

  • [ 1 ] [Wang, Shaozheng]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 2 ] [Zuo, Zongchao]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 3 ] [Ouyang, Zhangyi]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 4 ] [Liu, Xinyu]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 5 ] [Wang, Junke]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 6 ] [Shan, Yajun]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 7 ] [Meng, Ruoxi]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 8 ] [Zhao, Zhenhu]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 9 ] [Liu, Xiaolan]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 10 ] [Liu, Xiaoyan]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 11 ] [Jin, Yiguang]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 12 ] [Zhang, Hong]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 13 ] [Wang, Limei]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 14 ] [Cong, Yuwen]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China
  • [ 15 ] [Zuo, Zongchao]Beijing Univ Technol, Fac Environm & Life, 100 Pingleyuan, Beijing 100124, Peoples R China
  • [ 16 ] [Li, Zhongtang]Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China
  • [ 17 ] [Liu, Xinyu]Hebei Univ, Coll Life Sci, 180 Wusi East Rd, Baoding 071002, Peoples R China

Reprint Author's Address:

  • [Zhang, Hong]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China;;[Wang, Limei]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China;;[Cong, Yuwen]Beijing Inst Radiat Med, Dept Expt Hematol & Biochem, Beijing Key Lab Radiobiol, 27 Taiping Rd, Beijing 100850, Peoples R China

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Source :

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ISSN: 0006-291X

Year: 2024

Volume: 704

3 . 1 0 0

JCR@2022

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count: 1

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 1

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