2. Academic Validation
  3. Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production

Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production

  • Biochem Biophys Res Commun. 2024 Apr 16:704:149661. doi: 10.1016/j.bbrc.2024.149661.
Shaozheng Wang 1,  Zongchao Zuo 2,  Zhangyi Ouyang 1,  Xinyu Liu 3,  Junke Wang 1,  Yajun Shan 1,  Ruoxi Meng 1,  Zhenhu Zhao 1,  Xiaolan Liu 1,  Xiaoyan Liu 1,  Yiguang Jin 1,  Zhongtang Li 4,  Hong Zhang 5,  Limei Wang 6,  Yuwen Cong 7
Affiliations

Affiliations

  • 1 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China.
  • 2 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China; Faculty of Environment and Life, Beijing University of Technology, No.100, Pingleyuan, Chaoyang, 100124, Beijing, China.
  • 3 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China; College of Life Sciences, Hebei University, No.180 Wusi East Road, 071000, Baoding, China.
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No.38 Xueyuan Road, Haidian District, 100191, Beijing, China.
  • 5 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China. Electronic address: [email protected].
  • 6 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China. Electronic address: [email protected].
  • 7 Beijing Key Laboratory for Radiobiology, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No.27 Taiping Road, Haidian District, 100850, Beijing, China. Electronic address: [email protected].
PMID: 38417343 DOI: 10.1016/j.bbrc.2024.149661
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 °C, and would not be feasible in a mass casualty scenario where rapid and cost-effective intervention is crucial. Delta-tocotrienol (δ-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 δ-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 δ-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 BM-HSCs. In 4.0Gy irradiated nonhuman primates, δ-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 δ-T3H as a promising radiomitigator for the management of H-ARS, particularly in a mass casualty scenario.

Keywords

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

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