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Liver fibrotic development is reduced through inflammation prevention by an adenosine derivative compound
Mariana Domínguez-López1, Rebeca Pérez-Cabeza de Vaca2, Jesús Rafael Rodríguez-Aguilera1
1Instituto de Fisiología Celular, UNAM, Departamento de Biología Celular y Desarrollo, Laboratorio, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, 04510 México City, Mexico.
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.
Insights
Adenosine compound IFC-305 effectively reduced liver fibrosis and inflammation in rats. This compound regulates immune response, showing potential as a therapeutic strategy for liver damage.
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Liver fibrosis is a significant global health concern.
- Understanding its development is crucial for effective treatment strategies.
- Adenosine compounds are being investigated for therapeutic potential.
Purpose of the Study:
- To investigate the antifibrotic and anti-inflammatory effects of adenosine compound IFC-305.
- To evaluate IFC-305's impact on a carbon tetrachloride-induced liver fibrosis model in rats.
Main Methods:
- Utilized a carbon tetrachloride-induced liver fibrosis model in Wistar male rats.
- Assessed liver histology, macrophage populations (CD163+/CD11b/c+), and cytokine levels (MILLIPLEX MAP, ELISA).
- Quantified gene expression (RTqPCR), lipoperoxidation (TBARS), and reactive oxygen species (ROS) in Kupffer cells.
Main Results:
- IFC-305 significantly reduced liver fibrosis and inflammation at 6 and 8 weeks.
- Observed decreased collagen type 1 alpha 1 (Col1a1) expression and inflammatory cytokines (IL-1β, IL-6, MCP-1, TNF-α, IL-4).
- Showed reduced inflammatory macrophages, inhibited lipoperoxidation, and decreased ROS production.
Conclusions:
- IFC-305 inhibits liver fibrosis by modulating the immune response to carbon tetrachloride-induced damage.
- The immunomodulatory properties of IFC-305 suggest its potential as a therapeutic agent for preventing liver fibrosis.
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