Hepatic Stimulator Substance Alleviates Toxin-Induced and Immune-Mediated Liver Injury and Fibrosis in Rats

Background Liver fibrosis is a common scarring response to chronic liver injury. It is a precursor to cirrhosis and liver carcinoma. Hepatic stimulator substance (HSS), a known liver-specific but species-nonspecific growth factor, has been shown to protect hepatocytes from various toxins. Methods We have investigated the effects of HSS therapy on carbon tetrachloride (CCl 4 )-induced and porcine-serum-mediated hepatic injury and fibrosis. We hypothesize that HSS might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation. Results This report demonstrated that HSS therapy diminished α-smooth muscle actin expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. In addition, HSS treatment significantly protected the liver from injury by improving liver function tests and histological architecture of the liver. Conclusions These results provided novel insights into the mechanisms of HSS in the protection of the liver. Our results suggested that HSS might be a therapeutic antifibrotic agent for the treatment of liver fibrosis.