Therapeutic Potential of PDA@CeO2 in Suppressing Hepatic Stellate Cell Activation and Preventing Liver Fibrosis.

OBJECTIVE

Liver fibrosis replaces healthy tissue with scar tissue, potentially leading to cirrhosis and cancer. ROS drive this process by activating hepatic stellate cells. This study tests the hepatoprotective effects of PDA@CeO nanoparticles in scavenging ROS, inhibiting HSC activation, and delaying fibrosis, using 2D-SWE to assess treatment efficacy.

METHODS

In vitro, flow cytometry evaluated ROS levels in HSCs, scratch assays assessed migration, and α-SMA expression confirmed activation. In vivo, PDA@CeO NPs were tested in rats with CCl4-induced liver fibrosis, with effects monitored by 2D-SWE. Histopathological staining and fibrosis markers (Collagen I, α-SMA, TGF-β/Smad3, NOX4) assessed fibrosis progression.

RESULTS

In vitro, PDA@CeO reduced ROS levels and inhibited HSC migration, with decreased α-SMA expression indicating suppressed activation. In vivo, PDA@CeO treatment in CCl4-induced liver fibrosis rats reduced fibrosis markers. 2D-SWE showed improved liver stiffness, and histopathological analysis revealed reduced fibrosis and inflammation. The therapeutic effects were linked to modulation of the NOX4-TGF-β/Smad3 pathway, attenuating fibrosis progression.

CONCLUSION

This study demonstrates the potential of PDA@CeO NPs as a novel treatment for liver fibrosis. These nanoparticles scavenge ROS and modulate inflammatory pathways, targeting key signaling mechanisms like the NOX4-TGF-β/Smad3 pathway. PDA@CeO NPs offer a promising strategy for attenuating fibrosis at cellular and molecular levels. Additionally, 2D-SWE provides a non-invasive tool for monitoring therapeutic outcomes, positioning PDA@CeO NPs as a promising candidate for future clinical liver fibrosis treatments.