Cargando…

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model

Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP...

Descripción completa

Detalles Bibliográficos
Autores principales: Garg, Sarita, Garg, Tarun K., Miousse, Isabelle R., Wise, Stephen Y., Fatanmi, Oluseyi O., Savenka, Alena V., Basnakian, Alexei G., Singh, Vijay K., Hauer-Jensen, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598988/
https://www.ncbi.nlm.nih.gov/pubmed/36290618
http://dx.doi.org/10.3390/antiox11101895
_version_ 1784816484266016768
author Garg, Sarita
Garg, Tarun K.
Miousse, Isabelle R.
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Savenka, Alena V.
Basnakian, Alexei G.
Singh, Vijay K.
Hauer-Jensen, Martin
author_facet Garg, Sarita
Garg, Tarun K.
Miousse, Isabelle R.
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Savenka, Alena V.
Basnakian, Alexei G.
Singh, Vijay K.
Hauer-Jensen, Martin
author_sort Garg, Sarita
collection PubMed
description Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model.
format Online
Article
Text
id pubmed-9598988
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95989882022-10-27 Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model Garg, Sarita Garg, Tarun K. Miousse, Isabelle R. Wise, Stephen Y. Fatanmi, Oluseyi O. Savenka, Alena V. Basnakian, Alexei G. Singh, Vijay K. Hauer-Jensen, Martin Antioxidants (Basel) Article Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model. MDPI 2022-09-25 /pmc/articles/PMC9598988/ /pubmed/36290618 http://dx.doi.org/10.3390/antiox11101895 Text en © 2022 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
Garg, Sarita
Garg, Tarun K.
Miousse, Isabelle R.
Wise, Stephen Y.
Fatanmi, Oluseyi O.
Savenka, Alena V.
Basnakian, Alexei G.
Singh, Vijay K.
Hauer-Jensen, Martin
Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title_full Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title_fullStr Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title_full_unstemmed Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title_short Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model
title_sort effects of gamma-tocotrienol on partial-body irradiation-induced intestinal injury in a nonhuman primate model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598988/
https://www.ncbi.nlm.nih.gov/pubmed/36290618
http://dx.doi.org/10.3390/antiox11101895
work_keys_str_mv AT gargsarita effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT gargtarunk effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT miousseisabeller effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT wisestepheny effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT fatanmioluseyio effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT savenkaalenav effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT basnakianalexeig effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT singhvijayk effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel
AT hauerjensenmartin effectsofgammatocotrienolonpartialbodyirradiationinducedintestinalinjuryinanonhumanprimatemodel