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.
Highlights
Liver cancer is one of the most common causes of death worldwide (Sia et al, 2017)
We observed that granulocyte colony-stimulating factor (G-CSF) treatment prevented changes in the liver parenchyma up to 7 dpir (Figure 2A2), maintaining its homogeneous echogenicity and regular surface as similar to that found in the control group (Figures 2A–C)
We evaluated the benefits of G-CSF administration before and after irradiation exposure
Summary
Liver cancer is one of the most common causes of death worldwide (Sia et al, 2017). Liver cancer is understood as a multistep and complex disease resulting from many factors including chronic injury post hepatitis caused by B and C viral infections, liver cirrhosis, exacerbated alcohol consumption, and a high-fat diet (McGlynn et al, 2020). As a result of this common strategy, radiation-induced liver disease (RILD) has emerged such an adverse side effect of liver cancer treatment (Nakajima et al, 2018). As a result of liver radiotherapy exposition, several effects can occur, including vascular and neural system damage. These effects can promote disorders in the brain via the liver-brain inflammation axis and contributes to inflammatory diseases and alteration on patients’ behavior (D’Mello and Swain, 2011)
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