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

Biomed Pharmacother. 2023 Sep:165:115216. doi: 10.1016/j.biopha.2023.115216. Epub 2023 Aug 4.

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 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.

Keywords: Carbon tetrachloride; Collagen fibers; Cytokines; IFC-305; Kupffer cells; Liver fibrosis.

MeSH terms

  • Adenosine
  • Animals
  • Carbon Tetrachloride / toxicity
  • Cytokines / metabolism
  • Fibrosis
  • Inflammation* / metabolism
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / prevention & control
  • Liver*
  • Male
  • Rats
  • Rats, Wistar

Substances

  • Cytokines
  • Carbon Tetrachloride
  • Adenosine