Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production
Copyright © 2024 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:704 |
|---|---|
| Enthalten in: |
Biochemical and biophysical research communications - 704(2024) vom: 16. März, Seite 149661 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Shaozheng [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbrc.2024.149661 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369072553 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369072553 | ||
| 003 | DE-627 | ||
| 005 | 20240331001029.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbrc.2024.149661 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1357.xml |
| 035 | |a (DE-627)NLM369072553 | ||
| 035 | |a (NLM)38417343 | ||
| 035 | |a (PII)S0006-291X(24)00197-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Shaozheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sequential administration of delta-tocotrienol ameliorates radiation-induced myelosuppression in mice and non-human primates through inducing G-CSF production |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.03.2024 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Delta-tocotrienol | |
| 650 | 4 | |a Granulocyte colony-stimulating factor | |
| 650 | 4 | |a Hematopoietic acute radiation syndrome | |
| 650 | 4 | |a Nonhuman primates | |
| 650 | 4 | |a Radiation | |
| 650 | 4 | |a Radiomitigator | |
| 650 | 7 | |a Granulocyte Colony-Stimulating Factor |2 NLM | |
| 650 | 7 | |a 143011-72-7 |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a tocotrienol, delta |2 NLM | |
| 650 | 7 | |a 1SRB74OWSI |2 NLM | |
| 650 | 7 | |a Vitamin E |2 NLM | |
| 650 | 7 | |a 1406-18-4 |2 NLM | |
| 700 | 1 | |a Zuo, Zongchao |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Zhangyi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junke |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Yajun |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Ruoxi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhenhu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaolan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yiguang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhongtang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Limei |e verfasserin |4 aut | |
| 700 | 1 | |a Cong, Yuwen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical and biophysical research communications |d 1960 |g 704(2024) vom: 16. März, Seite 149661 |w (DE-627)NLM000000035 |x 1090-2104 |7 nnns |
| 773 | 1 | 8 | |g volume:704 |g year:2024 |g day:16 |g month:03 |g pages:149661 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbrc.2024.149661 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 704 |j 2024 |b 16 |c 03 |h 149661 | ||