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

放射治疗前使用粒细胞集落刺激因子治疗可预防小鼠放射性肝病

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作者: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 B

Abstract

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.

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