ANTI-FIBROTIC EFFECT OF HEPARIN, SILYMARIN AND ITS COMBINATION ON LIVER FIBROSIS MODEL IN RATS

Abstract

Liver fibrosis is the main complication of chronic liver disease. Various evidences suggest the role of thrombin in liver fibrogenesis either through its procoagulant function or its signaling via cell-surface receptors. Hence, the present study was undertaken to evaluate the effect of chronic thrombin inhibition by Heparin on experimentally induced chronic liver fibrosis in rats. Chronic liver fibrosis was induced in wistar rats by oral administration of carbon tetrachloride (CCl4) for seven weeks. Treatment with thrombin antagonist (Heparin), silymarin and its combination were started one week after the start of CCl4 intoxication for 6 weeks. After completion of treatment blood samples were collected and analyzed for liver function tests like SGOT, SGPT, ALP, total, direct and indirect bilirubin & total protein levels to assess liver function. Blood samples were also analyzed for blood coagulation parameters like fibrinogen levels. Area of liver fibrosis was quantified by histological studies of small portion of the excised liver. Serum GOT, GPT, ALP, total, direct and indirect bilirubin were found to be significantly higher in CCl4 intoxicated rats compared to normal control. Total protein was not significantly altered by CCl4 administration. Fibrinogen level was found to be significantly lower in CCl4 intoxicated rats as compared to normal control. Animals treated with heparin, silymarin and its combination for 6 weeks showed significantly lower SGOT, SGPT, ALP, total, direct and indirect bilirubin levels when compared with untreated CCl4 intoxicated rats (model control group). Fibrinogen level was significantly higher in all treatment groups than model control. Total protein level showed no significantly changes as compared to model control. Histological studies showed significantly lesser fibrosis area in all treatment groups as compared to model control group.