A new mouse model of radiation-induced liver disease reveals mitochondrial dysfunction as an underlying fibrotic stimulus

Melin, Nicolas; Yarahmadov, Tural; Sánchez-Taltavull, Daniel; Birrer, Fabienne; Brodie, Tess M.; Petit, Benoît; Felser, Andrea; Nuoffer, Jean‐Marc; Montani, M.; Vozenin, Marie-Catherine; Herrmann, Evelyn; Candinas, Daniel; Aebersold, Daniel M.; Stroka, Deborah

doi:10.1016/j.jhepr.2022.100508

Cited by 10 publications

(8 citation statements)

References 49 publications

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“…The liver is responsible for the metabolism of carbohydrates, proteins, fats, the biosynthesis of bile acids, and the biodegradation of bioactive substances such as hormones. Its function depends on the type and dynamics of the disease process that takes place in the cardiovascular system [34][35][36]. Therefore, cardiac irradiation and the occurrence of complications in the cardiovascular system may influence liver complications.…”

Section: Discussionmentioning

confidence: 99%

Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo

Łysek-Gładysińska,

Wieczorek,

Walaszczyk

et al. 2024

Metabolites

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The study aimed to investigate late radiation-induced changes in the histology, ultrastructure, and activity of lysosomal enzymes in mouse liver exposed to ionizing radiation. The experiment was conducted on C57BL/6J male mice whose distal part of the liver was exposed occasionally to single doses of radiation (6 MV photons) during targeted heart irradiation; estimated doses delivered to analyzed tissue were 0.025 Gy, 0.25 Gy, 1 Gy, and 2 Gy. Tissues were collected 40 weeks after irradiation. We have observed that late effects of radiation have an adaptive nature and their intensity was dose-dependent. Morphological changes in hepatocytes included an increased number of primary lysosomes and autophagic vacuoles, which were visible in tissues irradiated with 0.25 Gy and higher doses. On the other hand, a significant increase in the activity of lysosomal hydrolases was observed only in tissues exposed to 2 Gy. The etiology of these changes may be multifactorial and result, among others, from unintentional irradiation of the distal part of the liver and/or functional interaction of the liver with an irradiated heart. In conclusion, we confirmed the presence of late dose-dependent ultrastructural and biochemical changes in mouse hepatocytes after liver irradiation in vivo.

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Section: Discussionmentioning

confidence: 99%

Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo

Łysek-Gładysińska,

Wieczorek,

Walaszczyk

et al. 2024

Metabolites

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“…They observed that the proportion of neutrophils, macrophages, and T cells increased and that these cells preferentially clustered near the central veins after irradiation. Moreover collagen accumulated, indicating pericentral fibrosis [ 35 ]. Zabransky et al compared the TME, notably the immune infiltrate, in four different syngeneic hepatocellular carcinoma (HCC) mouse models treated with anti-PD-1 antibodies.…”

Section: Imc In Preclinical Researchmentioning

confidence: 99%

Single-cell high-dimensional imaging mass cytometry: one step beyond in oncology

et al. 2023

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Solid tumors have a dynamic ecosystem in which malignant and non-malignant (endothelial, stromal, and immune) cell types constantly interact. Importantly, the abundance, localization, and functional orientation of each cell component within the tumor microenvironment vary significantly over time and in response to treatment. Such intratumoral heterogeneity influences the tumor course and its sensitivity to treatments. Recently, high-dimensional imaging mass cytometry (IMC) has been developed to explore the tumor ecosystem at the single-cell level. In the last years, several studies demonstrated that IMC is a powerful tool to decipher the tumor complexity. In this review, we summarize the potential of this technology and how it may be useful for cancer research (from preclinical to clinical studies).

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“…Ferroptosis is a type of regulated cell death induced by lipid peroxidation, characterized by the depletion of glutathione and the decrease of glutathione peroxidase-4 (GPX4) activity. Specifically, lipid oxides cannot be metabolized through the glutathione reductase reaction catalyzed by GPX4, leading to the oxidation of lipids by divalent iron ions, producing ROS and the onset of ferroptosis ( Melin et al . 2022 ).…”

Section: Mechanisms Linking Radiation and Microbiotamentioning

confidence: 99%

Radiation injury and gut microbiota-based treatment

et al. 2023

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The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and•organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes ten common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation. Additionally, a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.

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A new mouse model of radiation-induced liver disease reveals mitochondrial dysfunction as an underlying fibrotic stimulus

Cited by 10 publications

References 49 publications

Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo

Late Effects of Ionizing Radiation on the Ultrastructure of Hepatocytes and Activity of Lysosomal Enzymes in Mouse Liver Irradiated In Vivo

Single-cell high-dimensional imaging mass cytometry: one step beyond in oncology

Radiation injury and gut microbiota-based treatment

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