In vivo inefficiency of pentoxifylline and interferon-alpha on hepatic fibrosis in biliary-obstructed rats: Assessment by tissue collagen content and prolidase activity

• Published in: Journal of gastroenterology and hepatology Vol. 18; no. 4; pp. 437 - 444
• Main Authors: TARÇIN, ORHAN, AVŞAR, KADİR, DEMİrtüRK, LEVENT, GÜLTEPE, MUSTAFA, OKTAR, BERNA K, ÖZDOğAN, OSMAN C, TARÇIN, ÖZLEM, BALOğLU, HÜSEYİN, GÜRBüZ, AHMET K
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01-04-2003; Blackwell Science
• Subjects: Animals; antifibrotic; bile duct ligation; Biological and medical sciences; Cholestasis - drug therapy; Cholestasis - enzymology; Cholestasis - pathology; Collagen - analysis; combination; combination, hepatic fibrosis; Dipeptidases - blood; Disease Models, Animal; Drug Therapy, Combination; Female; Gastroenterology. Liver. Pancreas. Abdomen; hepatic fibrosis; Immunologic Factors - administration & dosage; Immunologic Factors - therapeutic use; interferon-alpha; Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; Liver Cirrhosis - drug therapy; Liver Cirrhosis - enzymology; Liver Cirrhosis - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Other diseases. Semiology; pentoxifylline; Pentoxifylline - administration & dosage; Pentoxifylline - therapeutic use; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - therapeutic use; prolidase; rat; Rats; Rats, Wistar; Treatment Failure; Biliary tract; Vasodilator agent; Rat; Alpha interferon; Liver; Hepatic disease; Biliary tract disease; Obstruction; bile duct ligation; Immunotherapy; Complication; Xanthine derivatives; combination; Drug combination; Cytokine; Rodentia; Biological activity; Pentoxifylline; Vertebrata; Chemotherapy; Experimental disease; Mammalia; prolidase; Animal; Fibrosis; Digestive diseases; interferon-alpha; hepatic fibrosis; antifibrotic
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1046/j.1440-1746.2003.03004.x

Background and Aim: To evaluate the possible antifibrotic effects of two drugs, pentoxifylline (PTX) and interferon (IFN)‐α as well as their combination, on a bile‐duct‐ligated rat hepatic fibrosis model.
Methods: Bile ducts of 34 female Wistar rats were ligated, and 24 bile ducts were sham operated. Bile‐duct‐ligated rats were divided into four groups, in which either sterile saline, IFN‐α (100 000 IU/3 days a week), PTX (50 mg/kg/day) or IFN‐α + PTX were administered. Sham‐operated rats were treated at the same doses. On the 28th day, rats were decapitated to obtain blood for the measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ‐glutamyl transpeptidase (GGT) and bilirubins. Serum prolidase was assayed at the beginning and at the end of the study by the modified Chinard's colorimetric method. Liver prolidase was assayed after tissue homogenization. Liver collagen content was determined by the dye elution method described by Lopez de Leon. Morphometric‐densitometric measurements of hepatic fibrosis were quantified by computerized image analysis.
Results: The AST, ALT, ALP, GGT and bilirubins, liver prolidase enzyme activity, collagen content and hepatic collagen surface density were found to be increased in bile‐duct‐ligated rats on day 28. There was no statistically significant recovery or even a change in collagen turnover rate in rats treated with alternate regimens applied in the study (P > 0.05).
Conclusion: Pentoxifylline, IFN‐α and their combination have no beneficial effect on experimental fibrosis induced by biliary obstruction.
©  2003 Blackwell Publishing Asia Pty Ltd