| Abstract: | Background & Aim: We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro. Material & Methods: Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the GSEA analysis program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with TGFβ1 and PA, respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated. Results: Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including THBS1, ET-1, FN-1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the ROS pathway and decreased in the inflammatory response. Auranofin decreased NF-κB and IκBα in TGFβ1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation (BDL) model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a western diet (WD). Discussion: Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment. |
