Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact be...

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Autores principales:	Isalira Peroba Rezende Ramos, Marlon Lemos Dias, Alan Cesar Nunes De Moraes, Fernanda Guimarães Meireles Ferreira, Sergio Augusto Lopes Souza, Bianca Gutfilen, Thiago Barboza, Cibele Ferreira Pimentel, Cintia Marina Paz Batista, Tais Hanae Kasai-Brunswick, Fabio Da Silva De Azevedo Fortes, Cherley Borba Vieira De Andrade, Regina Coeli dos Santos Goldenberg
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	liver irradiation immunotherapy G-CSF alcohol ultrasonography Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/32e1ea3ca2f948629459a18832b3974e
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spelling	oai:doaj.org-article:32e1ea3ca2f948629459a18832b3974e2021-11-15T06:57:17ZGranulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice1663-981210.3389/fphar.2021.725084https://doaj.org/article/32e1ea3ca2f948629459a18832b3974e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.725084/fullhttps://doaj.org/toc/1663-9812Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.Isalira Peroba Rezende RamosMarlon Lemos DiasMarlon Lemos DiasAlan Cesar Nunes De MoraesFernanda Guimarães Meireles FerreiraSergio Augusto Lopes SouzaBianca GutfilenThiago BarbozaCibele Ferreira PimentelCibele Ferreira PimentelCibele Ferreira PimentelCibele Ferreira PimentelCintia Marina Paz BatistaTais Hanae Kasai-BrunswickTais Hanae Kasai-BrunswickTais Hanae Kasai-BrunswickFabio Da Silva De Azevedo FortesFabio Da Silva De Azevedo FortesCherley Borba Vieira De AndradeCherley Borba Vieira De AndradeRegina Coeli dos Santos GoldenbergRegina Coeli dos Santos GoldenbergFrontiers Media S.A.articleliverirradiationimmunotherapyG-CSFalcoholultrasonographyTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	liver irradiation immunotherapy G-CSF alcohol ultrasonography Therapeutics. Pharmacology RM1-950
spellingShingle	liver irradiation immunotherapy G-CSF alcohol ultrasonography Therapeutics. Pharmacology RM1-950 Isalira Peroba Rezende Ramos Marlon Lemos Dias Marlon Lemos Dias Alan Cesar Nunes De Moraes Fernanda Guimarães Meireles Ferreira Sergio Augusto Lopes Souza Bianca Gutfilen Thiago Barboza Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cintia Marina Paz Batista Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Fabio Da Silva De Azevedo Fortes Fabio Da Silva De Azevedo Fortes Cherley Borba Vieira De Andrade Cherley Borba Vieira De Andrade Regina Coeli dos Santos Goldenberg Regina Coeli dos Santos Goldenberg Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
description	Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.
format	article
author	Isalira Peroba Rezende Ramos Marlon Lemos Dias Marlon Lemos Dias Alan Cesar Nunes De Moraes Fernanda Guimarães Meireles Ferreira Sergio Augusto Lopes Souza Bianca Gutfilen Thiago Barboza Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cintia Marina Paz Batista Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Fabio Da Silva De Azevedo Fortes Fabio Da Silva De Azevedo Fortes Cherley Borba Vieira De Andrade Cherley Borba Vieira De Andrade Regina Coeli dos Santos Goldenberg Regina Coeli dos Santos Goldenberg
author_facet	Isalira Peroba Rezende Ramos Marlon Lemos Dias Marlon Lemos Dias Alan Cesar Nunes De Moraes Fernanda Guimarães Meireles Ferreira Sergio Augusto Lopes Souza Bianca Gutfilen Thiago Barboza Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cibele Ferreira Pimentel Cintia Marina Paz Batista Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Tais Hanae Kasai-Brunswick Fabio Da Silva De Azevedo Fortes Fabio Da Silva De Azevedo Fortes Cherley Borba Vieira De Andrade Cherley Borba Vieira De Andrade Regina Coeli dos Santos Goldenberg Regina Coeli dos Santos Goldenberg
author_sort	Isalira Peroba Rezende Ramos
title	Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
title_short	Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
title_full	Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
title_fullStr	Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
title_full_unstemmed	Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice
title_sort	granulocyte colony-stimulating factor treatment before radiotherapy protects against radiation-induced liver disease in mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/32e1ea3ca2f948629459a18832b3974e
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Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice

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