Effect of Chitosan‐Silver Nanoparticles on DEN‐induced Hepatocellular Injury by Regulation of Wnt/β‐Catenin and Apoptosis Signaling Pathways in Rats

Abstract

AbstractSilver nanoparticles (AgNPs) have gained remarkable attention as therapeutic agents since the appearance of nanotechnology. This study aims to assess the protective impact of chitosan‐silver nanoparticles (CS‐AgNPs) against DEN‐induced hepatocellular injury by regulation of Wnt/β‐Catenin and apoptosis signaling pathways in rats. CS‐AgNPs solutions were prepared by mixing different concentrations of chitosan and silver nitrate, and then subjected to gamma radiation at 20 kGy. The formation of CS‐AgNPs could be observed by naked eyes from the colour change from light yellow to reddish‐brown, and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Stability measurements confirmed that the prepared Cs‐AgNPs are highly stable for around 8 weeks. A crystal violet cytotoxicity assay of CS‐AgNPs has been detected in vitro on HepG2 hepatocellular carcinoma cell lines. The obtained results confirmed the selective influence of CS‐AgNPs on the HCC cell line in a time and dose dependent manner. Diethylnitrosamine (DEN) induced a marked increase in the expressions of Wnt, β‐Catenin, STAT3, MMP9, and Bcl‐2 with a significant decrease in the expression of BAX, p53, and P21. Additionally, DEN significantly decreased the levels of Cytc and TPTH while significantly increased the levels of COX‐2, PGE2, TGF‐1, AFP, and liver enzyme activity. The role of CS‐AgNPs is documented in diminishing the expressions of Wnt, β‐Catenin, STAT3, MMP9, and Bcl‐2. Also, CS‐AgNPs induced the decrease in the levels of COX‐2, PGE2, TGF‐1, AFP and liver enzyme activity accompanied by increased apoptosis. These results concluded that CS‐AgNPs might be a promising drug designed for treating liver diseases.