Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model
Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) mod...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16170 |
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| author | Tarun K. Garg Sarita Garg Isabelle R. Miousse Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Frits van Rhee Vijay K. Singh Martin Hauer-Jensen |
| author_facet | Tarun K. Garg Sarita Garg Isabelle R. Miousse Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Frits van Rhee Vijay K. Singh Martin Hauer-Jensen |
| author_sort | Tarun K. Garg |
| collection | DOAJ |
| description | Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. Importantly, GT3 accelerated the recovery in CD34<sup>+</sup> cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system. |
| first_indexed | 2024-03-09T16:19:15Z |
| format | Article |
| id | doaj.art-ef7776838a0b4613be3f43b6c959d0c1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:15Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ef7776838a0b4613be3f43b6c959d0c12023-11-24T15:34:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241617010.3390/ijms232416170Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate ModelTarun K. Garg0Sarita Garg1Isabelle R. Miousse2Stephen Y. Wise3Alana D. Carpenter4Oluseyi O. Fatanmi5Frits van Rhee6Vijay K. Singh7Martin Hauer-Jensen8UAMS Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADivision of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USAUAMS Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADivision of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADivision of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USARadiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. Importantly, GT3 accelerated the recovery in CD34<sup>+</sup> cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system.https://www.mdpi.com/1422-0067/23/24/16170colony-forming unitsgamma-tocotrienolhematopoietic progenitorsnonhuman primatesradiation countermeasuretotal-body irradiation |
| spellingShingle | Tarun K. Garg Sarita Garg Isabelle R. Miousse Stephen Y. Wise Alana D. Carpenter Oluseyi O. Fatanmi Frits van Rhee Vijay K. Singh Martin Hauer-Jensen Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model International Journal of Molecular Sciences colony-forming units gamma-tocotrienol hematopoietic progenitors nonhuman primates radiation countermeasure total-body irradiation |
| title | Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model |
| title_full | Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model |
| title_fullStr | Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model |
| title_full_unstemmed | Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model |
| title_short | Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model |
| title_sort | gamma tocotrienol modulates total body irradiation induced hematopoietic injury in a nonhuman primate model |
| topic | colony-forming units gamma-tocotrienol hematopoietic progenitors nonhuman primates radiation countermeasure total-body irradiation |
| url | https://www.mdpi.com/1422-0067/23/24/16170 |
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