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)-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. [ABSTRACT FROM AUTHOR]