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Volume 15
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10.3390/metabo15080546
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation

by
Alana D. Carpenter
1,2,
Yaoxiang Li
3,
Benjamin E. Packer
1,2,
Oluseyi O. Fatanmi
1,2,
Stephen Y. Wise
1,2,
Sarah A. Petrus
1,2,
Martin Hauer-Jensen
4,
Amrita K. Cheema
3,5 and
Vijay K. Singh
1,2,*
1
Division of Radioprotectants, Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
2
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
3
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
4
Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
5
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA
*
Author to whom correspondence should be addressed.
Metabolites 2025, 15(8), 546; https://doi.org/10.3390/metabo15080546
Submission received: 18 July 2025 / Revised: 1 August 2025 / Accepted: 8 August 2025 / Published: 12 August 2025
(This article belongs to the Section Advances in Metabolomics)
Versions Notes

Abstract

Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 hours (h), 8 h, 12 h, 1 d, 2, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points.
Keywords: GT3; biomarkers; metabolomics; nonhuman primates; radioprotection; partial-body irradiation; total-body irradiation GT3; biomarkers; metabolomics; nonhuman primates; radioprotection; partial-body irradiation; total-body irradiation

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MDPI and ACS Style

Carpenter, A.D.; Li, Y.; Packer, B.E.; Fatanmi, O.O.; Wise, S.Y.; Petrus, S.A.; Hauer-Jensen, M.; Cheema, A.K.; Singh, V.K. Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation. Metabolites 2025, 15, 546. https://doi.org/10.3390/metabo15080546

AMA Style

Carpenter AD, Li Y, Packer BE, Fatanmi OO, Wise SY, Petrus SA, Hauer-Jensen M, Cheema AK, Singh VK. Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation. Metabolites. 2025; 15(8):546. https://doi.org/10.3390/metabo15080546

Chicago/Turabian Style

Carpenter, Alana D., Yaoxiang Li, Benjamin E. Packer, Oluseyi O. Fatanmi, Stephen Y. Wise, Sarah A. Petrus, Martin Hauer-Jensen, Amrita K. Cheema, and Vijay K. Singh. 2025. "Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation" Metabolites 15, no. 8: 546. https://doi.org/10.3390/metabo15080546

APA Style

Carpenter, A. D., Li, Y., Packer, B. E., Fatanmi, O. O., Wise, S. Y., Petrus, S. A., Hauer-Jensen, M., Cheema, A. K., & Singh, V. K. (2025). Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation. Metabolites, 15(8), 546. https://doi.org/10.3390/metabo15080546

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