Liver fibrotic development is reduced through inflammation prevention by an adenosine derivative compound - 13/08/23
Abstract |
Background |
Liver fibrosis is a global health problem, and studying its development provides important information to address its treatment. Here, we characterized the effects of an adenosine compound (IFC-305) on preventing fibrosis and liver inflammation. Methods : We studied the impact of IFC-305 on a carbon tetrachloride-induced liver fibrosis model in Wistar male rats at 4, 6, and 8 weeks. The effects were characterized by liver tissue histology, macrophages identification by flow cytometry with CD163+/CD11b/c+ antibodies, hepatic and plasmatic cytokine levels employing MILLIPLEX MAP and ELISA, Col1a1 and Il6 gene expression by RT - qPCR, lipoperoxidation by TBARS reaction, and reactive oxygen species using 2'−7'dichlorofluorescin diacetate. Results : CCl 4 -induced liver fibrosis and inflammation were significantly reduced in rats treated with IFC-305 at 6 and 8 weeks. In addition, we observed diminished expression of Col1a1 ; a decrease in the inflammatory cytokines IL-1β, IL-6, MCP-1, TNF-α, and IL-4 a; reduction in inflammatory macrophages; inhibition of lipoperoxidation; and ROS production in Kupffer cells. Conclusion : This study showed that IFC-305 can inhibit liver fibrosis establishment by regulating the immune response during CCl 4 -induced damage. The immunomodulatory action of IFC-305 supports its use as a potential therapeutic strategy for preventing liver fibrosis.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Kinetics of the anti-fibrotic activity of IFC-305 in rats administered with CCl 4 and CCl 4 +IFC-305 at 4, 6, and 8 weeks. In the groups treated with CCl 4 , there were increases in collagen fibers; the fibrogenic cytokine IL-6; the pro-inflammatory cytokines IL-1β, TNF-α, MCP-1; and the expression of Col1a1 , the main marker of liver fibrosis. Likewise, there was an increase in M1 inflammatory macrophages. The increase in these markers shows the relationship between the development of fibrosis and the inflammatory response. On the other hand, the concomitant treatment of rats with IFC-305 showed a decrease in all these fibrosis markers in the liver, revealing the anti-fibrotic and anti-inflammatory activity of the hepatoprotective compound IFC-305. Furthermore, the decrease in these markers correlated with the increase in anti-inflammatory M2 macrophages. These results lead to the proposed use of IFC-305 as a potential early treatment to inhibit the development of fibrotic diseases mediated by regulating the immune response (Created in BioRender.com).
Kinetics of the anti-fibrotic activity of IFC-305 in rats administered with CCl 4 and CCl 4 +IFC-305 at 4, 6, and 8 weeks. In the groups treated with CCl 4 , there were increases in collagen fibers; the fibrogenic cytokine IL-6; the pro-inflammatory cytokines IL-1β, TNF-α, MCP-1; and the expression of Col1a1 , the main marker of liver fibrosis. Likewise, there was an increase in M1 inflammatory macrophages. The increase in these markers shows the relationship between the development of fibrosis and the inflammatory response. On the other hand, the concomitant treatment of rats with IFC-305 showed a decrease in all these fibrosis markers in the liver, revealing the anti-fibrotic and anti-inflammatory activity of the hepatoprotective compound IFC-305. Furthermore, the decrease in these markers correlated with the increase in anti-inflammatory M2 macrophages. These results lead to the proposed use of IFC-305 as a potential early treatment to inhibit the development of fibrotic diseases mediated by regulating the immune response (Created in BioRender.com). ga1 Le texte complet de cet article est disponible en PDF.
Highlights |
• | IFC-305 decreases inflammatory M1 macrophages during fibrosis development. |
• | IFC-305 decreases inflammatory cytokine IL-1β and profibrogenic cytokine IL-6 in both plasma and liver, manifesting its immunomodulatory activity. |
• | IFC-305 regenerates liver architecture during fibrosis progression. |
• | IFC-305 reduces reactive oxygen species in primary cultures of Kupffer cells, demonstrating its antioxidant activity. |
Abbreviations : IFC, KCs, IL, TNF-α, MCP-1, DCFH-DA, MDA, ROS, CCl 4
Keywords : Liver fibrosis, Carbon tetrachloride, IFC-305, Collagen fibers, Cytokines, Kupffer cells
Plan
Vol 165
Article 115216- septembre 2023 Retour au numéro
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