title: Antifibrotic effect of heparin on liver fibrosis model in rats.
abstract: OBJECTIVE
  To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats.
  
  
  METHODS
  Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl4) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically.
  
  
  RESULTS
  Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.
  
  
  CONCLUSIONS
  Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.
authors.affiliation: Binita Shah, Gaurang Shah, Department of Pharmacology, K B Institute of Pharmaceutical Education and Research, Gandhinagar 382023, Gujarat, India.
authors.forename: Binita
authors.initials: B
authors.lastname: Shah
authors.forename: Gaurang
authors.initials: G
authors.lastname: Shah
keywords: Carbon tetrachloride; Heparin; Hepatic dysfunction; Liver fibrosis; Thrombin antagonist