Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury

Radiation injury will result in multiorgan dysfuntion leading to multiorgan failure. In addition to many factors such as radiation dose, dose rate, the severity of the injury will also depend on organ systems which are exposed. Here, we report the protective property of gamma tocotrienol (GT3) in to...

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Autores principales: Vidya P. Kumar, Sasha Stone, Shukla Biswas, Neel Sharma, Sanchita P. Ghosh
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Publicado: Frontiers Media S.A. 2020
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spelling oai:doaj.org-article:dbfc01995d6a4714856cc667a1a96b882021-12-01T03:28:41ZGamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury1663-981210.3389/fphar.2020.587970https://doaj.org/article/dbfc01995d6a4714856cc667a1a96b882020-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2020.587970/fullhttps://doaj.org/toc/1663-9812Radiation injury will result in multiorgan dysfuntion leading to multiorgan failure. In addition to many factors such as radiation dose, dose rate, the severity of the injury will also depend on organ systems which are exposed. Here, we report the protective property of gamma tocotrienol (GT3) in total as well as partial body irradiation (PBI) model in C3H/HeN male mice. We have carried out PBI by targeting thoracic region (lung-PBI) using Small Animal Radiation Research Platform, an X-ray irradiator with capabilities of an image guided irradiation with a variable collimator with minimized exposure to non-targeted tissues and organs. Precise and accurate irradiation of lungs was carried out at either 14 or 16 Gy at an approximate dose rate of 2.6 Gy/min. Though a low throughput model, it is amenable to change the field size on the spot. No damage to other non-targeted organs was observed in histopathological evaluation. There was no significant change in peripheral blood counts of irradiated mice in comparison to naïve mice. Femoral bone marrow cells had no damage in irradiated mice. As expected, damage to the targeted tissue was observed in the histopathological evaluation and non-targeted tissue was found normal. Regeneration and increase of cellularity and megakaryocytes on GT3 treatment was compared to significant loss of cellularity in saline group. Peak alveolitis was observed on day 14 post-PBI and protection from alveolitis by GT3 was noted. In irradiated lung tissue, thirty proteins were found to be differentially expressed but modulated by GT3 to reverse the effects of irradiation. We propose that possible mode of action of GT3 could be Angiopoietin 2-Tie2 pathway leading to AKT/ERK pathways resulting in disruption in cell survival/angiogenesis.Vidya P. KumarSasha StoneShukla BiswasNeel SharmaSanchita P. GhoshFrontiers Media S.A.articlegamma tocotrienolpartial body irradiationsmall animal radiation research platformradiation injury to normal lungsprophylactic treatmentThoracic irradiationTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 11 (2020)
institution DOAJ
collection DOAJ
language EN
topic gamma tocotrienol
partial body irradiation
small animal radiation research platform
radiation injury to normal lungs
prophylactic treatment
Thoracic irradiation
Therapeutics. Pharmacology
RM1-950
spellingShingle gamma tocotrienol
partial body irradiation
small animal radiation research platform
radiation injury to normal lungs
prophylactic treatment
Thoracic irradiation
Therapeutics. Pharmacology
RM1-950
Vidya P. Kumar
Sasha Stone
Shukla Biswas
Neel Sharma
Sanchita P. Ghosh
Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
description Radiation injury will result in multiorgan dysfuntion leading to multiorgan failure. In addition to many factors such as radiation dose, dose rate, the severity of the injury will also depend on organ systems which are exposed. Here, we report the protective property of gamma tocotrienol (GT3) in total as well as partial body irradiation (PBI) model in C3H/HeN male mice. We have carried out PBI by targeting thoracic region (lung-PBI) using Small Animal Radiation Research Platform, an X-ray irradiator with capabilities of an image guided irradiation with a variable collimator with minimized exposure to non-targeted tissues and organs. Precise and accurate irradiation of lungs was carried out at either 14 or 16 Gy at an approximate dose rate of 2.6 Gy/min. Though a low throughput model, it is amenable to change the field size on the spot. No damage to other non-targeted organs was observed in histopathological evaluation. There was no significant change in peripheral blood counts of irradiated mice in comparison to naïve mice. Femoral bone marrow cells had no damage in irradiated mice. As expected, damage to the targeted tissue was observed in the histopathological evaluation and non-targeted tissue was found normal. Regeneration and increase of cellularity and megakaryocytes on GT3 treatment was compared to significant loss of cellularity in saline group. Peak alveolitis was observed on day 14 post-PBI and protection from alveolitis by GT3 was noted. In irradiated lung tissue, thirty proteins were found to be differentially expressed but modulated by GT3 to reverse the effects of irradiation. We propose that possible mode of action of GT3 could be Angiopoietin 2-Tie2 pathway leading to AKT/ERK pathways resulting in disruption in cell survival/angiogenesis.
format article
author Vidya P. Kumar
Sasha Stone
Shukla Biswas
Neel Sharma
Sanchita P. Ghosh
author_facet Vidya P. Kumar
Sasha Stone
Shukla Biswas
Neel Sharma
Sanchita P. Ghosh
author_sort Vidya P. Kumar
title Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
title_short Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
title_full Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
title_fullStr Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
title_full_unstemmed Gamma Tocotrienol Protects Mice From Targeted Thoracic Radiation Injury
title_sort gamma tocotrienol protects mice from targeted thoracic radiation injury
publisher Frontiers Media S.A.
publishDate 2020
url https://doaj.org/article/dbfc01995d6a4714856cc667a1a96b88
work_keys_str_mv AT vidyapkumar gammatocotrienolprotectsmicefromtargetedthoracicradiationinjury
AT sashastone gammatocotrienolprotectsmicefromtargetedthoracicradiationinjury
AT shuklabiswas gammatocotrienolprotectsmicefromtargetedthoracicradiationinjury
AT neelsharma gammatocotrienolprotectsmicefromtargetedthoracicradiationinjury
AT sanchitapghosh gammatocotrienolprotectsmicefromtargetedthoracicradiationinjury
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