The Effect Of Interferon Alone Or Combined With Silymarin On Liver And Bone Parameters In Bile Duct Ligated Rats

Thirty-six rats with biliary obstruction induced by double ligation and section of the common bile duct were randomly and blindly assigned to receive subcutaneous injection of interferon alpha (INF-alpha at 6750 or 13500 IU/kg) three times weekly alone, a combination of INF-alpha and silymarin (25 mg/kg once a day orally) or saline, starting one day after surgery and continued for one month. At the end of the treatment period, rats were killed and analyzed for blood biochemistry, liver and bone histopathology. The administration of INF-alpha at 6750 IU/kg increased plasma aspartate aminotransferase by 60.6%. Serum alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase activities were markedly raised after INF-alpha 13500 U/kg by 74.6%, 89% and 109%, respectively. Such elevations in liver enzymes were not observed in rats treated with a combination of INF-alpha and silymarin. Serum bilirubin decreased by 30.8 and 36.1% after treatment with INF-alpha at 6750 and 13500 IU/kg and by 23.7 and 20.8% after treatment with INF-alpha at 6750 or 13500 IU/kg combined with silymarin, respectively. Calcium levels in plasma were not significantly altered by INF-alpha alone or combined with silymarin. On histology, INF-alpha at 6750 IU/kg failed to prevent fibrosis in liver of BDL rats, although many of the hepatocytes appeared normal, while the higher dose of resulted in some improvement in the degree of fibrosis, oedema and lymphocytic infiltration. The addition of silymarin to interferon did not result in further histological improvement. In contrast to observations in the liver, thickness of bone tissue at the diaphysis of tibia was reduced in BDL rats, but restored to normal values by treatment with INFalpha alone or by the combination of INF-alpha and silymarin. The high dose of interferon either alone or accompanied with silymarin made much improvement in the bone changes that resulted from bile duct legation These results suggest that INFalpha alone or co-administered with silymarin is of limited value in this model of cholestatic liver injury, but appear to prevent bone alterations in obstructive jaundice INF-alpha is likely to exert antifibrotic effects distinct from its antiviral properties. The study also indicates that bile duct ligation is a reliable and efficient model for producing osteoporosis in rats for the assessment of different drugs and pathophysiologic mechanisms involved.