Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure

Abstract To date, the United States Food and Drug Administration (FDA) has approved four drugs to mitigate hematopoietic acute radiation syndrome and all four are repurposed radiomitigators. There are several additional drug candidates currently under evaluation that may also be helpful for use duri...

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Autores principales:	Yaoxiang Li, Michael Girgis, Stephen Y. Wise, Oluseyi O. Fatanmi, Thomas M. Seed, Manoj Maniar, Amrita K. Cheema, Vijay K. Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80b88c81ca084e9ba1188c3b3a5941af
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spelling	oai:doaj.org-article:80b88c81ca084e9ba1188c3b3a5941af2021-12-02T15:02:23ZAnalysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure10.1038/s41598-021-91067-92045-2322https://doaj.org/article/80b88c81ca084e9ba1188c3b3a5941af2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91067-9https://doaj.org/toc/2045-2322Abstract To date, the United States Food and Drug Administration (FDA) has approved four drugs to mitigate hematopoietic acute radiation syndrome and all four are repurposed radiomitigators. There are several additional drug candidates currently under evaluation that may also be helpful for use during a widespread emergency. One possible candidate is Ex-Rad, also known as ON01210, a chlorobenzyl sulfone derivative (organosulfur compound), which is a novel, small-molecule kinase inhibitor with demonstrated efficacy in the murine model. In this study, we have evaluated the metabolomic and lipidomic profiles in serum samples of nonhuman primates (NHPs) treated with Ex-Rad after exposure to ionizing radiation. Two different dose administration schedules (Ex-Rad I administered 24 and 36 h post-irradiation, and Ex-Rad II administered 48 and 60 h post-irradiation), were used and evaluated using a global molecular profiling approach. We observed alterations in biochemical pathways relating to inflammation and oxidative stress after radiation exposure that were alleviated in animals that received Ex-Rad I or Ex-Rad II. The results from this study lend credence to the possible radiomitigative effects of this drug possibly via a dampening of metabolism-based tissue injury, thus aiding in recovery of vital, radiation-injured organ systems.Yaoxiang LiMichael GirgisStephen Y. WiseOluseyi O. FatanmiThomas M. SeedManoj ManiarAmrita K. CheemaVijay K. SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yaoxiang Li Michael Girgis Stephen Y. Wise Oluseyi O. Fatanmi Thomas M. Seed Manoj Maniar Amrita K. Cheema Vijay K. Singh Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
description	Abstract To date, the United States Food and Drug Administration (FDA) has approved four drugs to mitigate hematopoietic acute radiation syndrome and all four are repurposed radiomitigators. There are several additional drug candidates currently under evaluation that may also be helpful for use during a widespread emergency. One possible candidate is Ex-Rad, also known as ON01210, a chlorobenzyl sulfone derivative (organosulfur compound), which is a novel, small-molecule kinase inhibitor with demonstrated efficacy in the murine model. In this study, we have evaluated the metabolomic and lipidomic profiles in serum samples of nonhuman primates (NHPs) treated with Ex-Rad after exposure to ionizing radiation. Two different dose administration schedules (Ex-Rad I administered 24 and 36 h post-irradiation, and Ex-Rad II administered 48 and 60 h post-irradiation), were used and evaluated using a global molecular profiling approach. We observed alterations in biochemical pathways relating to inflammation and oxidative stress after radiation exposure that were alleviated in animals that received Ex-Rad I or Ex-Rad II. The results from this study lend credence to the possible radiomitigative effects of this drug possibly via a dampening of metabolism-based tissue injury, thus aiding in recovery of vital, radiation-injured organ systems.
format	article
author	Yaoxiang Li Michael Girgis Stephen Y. Wise Oluseyi O. Fatanmi Thomas M. Seed Manoj Maniar Amrita K. Cheema Vijay K. Singh
author_facet	Yaoxiang Li Michael Girgis Stephen Y. Wise Oluseyi O. Fatanmi Thomas M. Seed Manoj Maniar Amrita K. Cheema Vijay K. Singh
author_sort	Yaoxiang Li
title	Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
title_short	Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
title_full	Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
title_fullStr	Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
title_full_unstemmed	Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure
title_sort	analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with ex-rad, a radiation countermeasure
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/80b88c81ca084e9ba1188c3b3a5941af
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Analysis of the metabolomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation countermeasure

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