Alpha-interferon prevents liver collagen deposition and damage induced by prolonged bile duct obstruction in the rat.
OBJECTIVE
Interferons have been used to treat chronic viral hepatitis, due to their antiviral properties. However, interferons are now recognized also to inhibit collagen production. Since fibrosis has been associated with liver damage and dysfunction, the effects of interferon-alpha 2 b on biliary obstruction-induced fibrosis were investigated.


METHODS
Extrahepatic cholestasis was induced in male Wistar rats (around 200g) by double ligation and division of the common bile duct. Control rats were sham operated. Interferon-alpha 2b (IFN-alpha; 100,000 IU/rat) was administered subcutaneously, daily after surgery. The animals were killed after 4 weeks of bile duct ligation or sham operation. Liver damage and cholestasis was analyzed by histological, ultrastructural and biochemical techniques.


RESULTS
Biliary obstruction produced dilation of the bile canaliculi, disorganization of mitochondria and an increase in vacuolization. Bile duct ligation led to an important accumulation of collagen, determined, both histologically and as the hydroxyproline content of the liver. Bilirubin and serum enzyme activities (determined as markers of cholestasis) increased several-fold after bile duct ligation. Administration of IFN-alpha to bile duct ligated rats resulted in significant preservation of ultrastructure, histology, inhibition of collagen accumulation and in a partial improvement of serum markers of cholestasis.


CONCLUSIONS
It is concluded that interferons possess interesting beneficial effects on the liver not related to its antiviral properties but probably associated with its antifibrogenic properties.
Muriel
P
P
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados del I.P.N. México, D.F. México.
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins
D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008112:Liver Glycogen; D011994:Recombinant Proteins; D003094:Collagen