Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Metabolomic Changes in Plasma of Preterminal Stage of Rhesus Nonhuman Primates Exposed to Lethal Dose of Radiation

Alana D. Carpenter
,
Oluseyi O Fatanmi
ORCID logo ,
Stephen Y Wise
,
Sarah A. Petrus
,
John B. Tyburski
,
Amrita K Cheema
ORCID logo ,
Vijay K Singh
* ORCID logo
Version 1 : Received: 21 November 2023 / Approved: 22 November 2023 / Online: 22 November 2023 (13:47:20 CET)

A peer-reviewed article of this Preprint also exists.

Carpenter, A.D.; Fatanmi, O.O.; Wise, S.Y.; Petrus, S.A.; Tyburski, J.B.; Cheema, A.K.; Singh, V.K. Metabolomic Changes in Plasma of Preterminal Stage of Rhesus Nonhuman Primates Exposed to Lethal Dose of Radiation. Metabolites 2024, 14, 18. Carpenter, A.D.; Fatanmi, O.O.; Wise, S.Y.; Petrus, S.A.; Tyburski, J.B.; Cheema, A.K.; Singh, V.K. Metabolomic Changes in Plasma of Preterminal Stage of Rhesus Nonhuman Primates Exposed to Lethal Dose of Radiation. Metabolites 2024, 14, 18.

Abstract

Ionizing radiation exposure is known to induce molecular and cellular injury, inflicting a cascade of potentially catastrophic events leading to tissue and organ damage. Metabolomic analysis allows for the identification and quantification of small molecules downstream of genomic changes induced by radiation exposure. We aimed to characterize metabolomic changes that underscore the prefinal stage of lethally irradiated rhesus nonhuman primates (NHPs). Peripheral blood was drawn at baseline, post-exposure as well as at the preterminal stage of NHPs (immediately prior to death in moribund NHPs), which did not survive exposure with 7.2 Gy total-body radiation (LD70/60). Herein, we analyzed global metabolomic changes using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in plasma samples of NHPs collected at various timepoints in relation to irradiation. The overall goal was to identify metabolic shifts present immediately prior to death. Our findings, for the first time, show that radiation induced significant time dependent metabolic perturbations when compared to pre-irradiation samples, particularly in the glycerophospholipid metabolism and steroid hormone biosynthesis and metabolism pathways. These findings provide valuable insights for identifying biomarkers for lethality, which may be helpful for triage during a mass casualty scenario.

Keywords

Biomarkers; metabolomics; nonhuman primates; preterminal; total-body irradiation

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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