Liver fibrotic development is reduced through inflammation prevention by an adenosine derivative compound

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 RTqPCR, lipoperoxidation by TBARS reaction, and reactive oxygen species using 2'−7'dichlorofluorescin diacetate. Results: CCl4-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 CCl4-induced damage. The immunomodulatory action of IFC-305 supports its use as a potential therapeutic strategy for preventing liver fibrosis. [Display omitted] •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.