Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-β1 (TGF-β1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl4-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-β1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.
Keywords: Hepatic fibrosis; Hepatic stellate cells; Roxarsone; TGF-β1/Smad.
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