In vivo inefficiency of pentoxifylline and interferon-alpha on hepatic fibrosis in biliary-obstructed rats: assessment by tissue collagen content and prolidase activity.
OBJECTIVE
To evaluate the possible antifibrotic effects of two drugs, pentoxifylline (PTX) and interferon (IFN)-alpha 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-alpha (100 000 IU/3 days a week), PTX (50 mg/kg/day) or IFN-alpha + 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), gamma-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).


CONCLUSIONS
Pentoxifylline, IFN-alpha and their combination have no beneficial effect on experimental fibrosis induced by biliary obstruction.
Tarçin
Orhan
O
Department of Gastroenterology, Gülhane Military Academy, Haydarpaşa Educational Hospital, Istanbul, Turkey. ortarcin@hotmail.com
Avşar
Kadir
K
Demirtürk
Levent
L
Gültepe
Mustafa
M
Oktar
Berna K
BK
Ozdoğan
Osman C
OC
Tarçin
Ozlem
O
Baloğlu
Hüseyin
H
Gürbüz
Ahmet K
AK
D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D003094:Collagen / Q000032:analysis*; D004150:Dipeptidases / Q000097:blood*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017211:Treatment Failure
D007155:Immunologic Factors; D016898:Interferon-alpha; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase; D010431:Pentoxifylline