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PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress

The development of safe, orally available, and effective prophylactic countermeasures to protect our warfighters is an unmet need because there is no such FDA-approved countermeasure available for use. Th 1-Propanethiol, 3-(methylamino)-2-((methylamino)methyl) (PrC-210), a synthetic small molecule,...

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Autores principales: Kumar, Vidya P., Biswas, Shukla, Holmes-Hampton, Gregory P., Goesch, Torsten, Fahl, William, Ghosh, Sanchita P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376632/
https://www.ncbi.nlm.nih.gov/pubmed/37507957
http://dx.doi.org/10.3390/antiox12071417
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author Kumar, Vidya P.
Biswas, Shukla
Holmes-Hampton, Gregory P.
Goesch, Torsten
Fahl, William
Ghosh, Sanchita P.
author_facet Kumar, Vidya P.
Biswas, Shukla
Holmes-Hampton, Gregory P.
Goesch, Torsten
Fahl, William
Ghosh, Sanchita P.
author_sort Kumar, Vidya P.
collection PubMed
description The development of safe, orally available, and effective prophylactic countermeasures to protect our warfighters is an unmet need because there is no such FDA-approved countermeasure available for use. Th 1-Propanethiol, 3-(methylamino)-2-((methylamino)methyl) (PrC-210), a synthetic small molecule, is a member of a new family of aminothiols designed to reduce toxicity while scavenging reactive oxygen species (ROS). Our study investigated the protective role of a single oral administration of PrC-210 against radiation-induced hematopoietic and intestinal injury in mice. Pre-treatment with PrC-210 significantly improved the survival of mice exposed to a lethal dose of radiation. Our findings indicated that the radioprotective properties of PrC-210 are achieved by accelerating the recovery of the hematopoietic system, stimulating bone marrow progenitor cells, and ameliorating additional biomarkers of hematopoietic injury. PrC-210 pre-treatment reduced intestinal injury in mice exposed to a lethal dose of radiation by restoring jejunal crypts and villi, reducing translocation of bacteria to the spleen, maintaining citrulline levels, and reducing the sepsis marker serum amyloid A (SAA) in serum. Finally, PrC-210 pre-treatment led to a significant reduction (~10 fold) of Nos2 expression (inducible nitric oxide) in the spleen and decreased oxidative stress by enhancing the antioxidant defense system. These data support the further development of PrC-210 to receive approval from the FDA to protect warfighters and first responders from exposure to the harmful effects of ionizing radiation.
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spelling pubmed-103766322023-07-29 PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress Kumar, Vidya P. Biswas, Shukla Holmes-Hampton, Gregory P. Goesch, Torsten Fahl, William Ghosh, Sanchita P. Antioxidants (Basel) Article The development of safe, orally available, and effective prophylactic countermeasures to protect our warfighters is an unmet need because there is no such FDA-approved countermeasure available for use. Th 1-Propanethiol, 3-(methylamino)-2-((methylamino)methyl) (PrC-210), a synthetic small molecule, is a member of a new family of aminothiols designed to reduce toxicity while scavenging reactive oxygen species (ROS). Our study investigated the protective role of a single oral administration of PrC-210 against radiation-induced hematopoietic and intestinal injury in mice. Pre-treatment with PrC-210 significantly improved the survival of mice exposed to a lethal dose of radiation. Our findings indicated that the radioprotective properties of PrC-210 are achieved by accelerating the recovery of the hematopoietic system, stimulating bone marrow progenitor cells, and ameliorating additional biomarkers of hematopoietic injury. PrC-210 pre-treatment reduced intestinal injury in mice exposed to a lethal dose of radiation by restoring jejunal crypts and villi, reducing translocation of bacteria to the spleen, maintaining citrulline levels, and reducing the sepsis marker serum amyloid A (SAA) in serum. Finally, PrC-210 pre-treatment led to a significant reduction (~10 fold) of Nos2 expression (inducible nitric oxide) in the spleen and decreased oxidative stress by enhancing the antioxidant defense system. These data support the further development of PrC-210 to receive approval from the FDA to protect warfighters and first responders from exposure to the harmful effects of ionizing radiation. MDPI 2023-07-13 /pmc/articles/PMC10376632/ /pubmed/37507957 http://dx.doi.org/10.3390/antiox12071417 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kumar, Vidya P.
Biswas, Shukla
Holmes-Hampton, Gregory P.
Goesch, Torsten
Fahl, William
Ghosh, Sanchita P.
PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title_full PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title_fullStr PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title_full_unstemmed PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title_short PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress
title_sort prc-210 protects against radiation-induced hematopoietic and intestinal injury in mice and reduces oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376632/
https://www.ncbi.nlm.nih.gov/pubmed/37507957
http://dx.doi.org/10.3390/antiox12071417
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