The effects of pegylated interferon alpha 2b on bile-duct ligation induced liver fibrosis in rats

Ann Hepatol. 2009 Jul-Sep;8(3):234-40.

Abstract

Objective: To test the effects of peginterferon in an unrecoverable model of bile-duct ligation (BDL) induced liver fibrosis.

Material and methods: Thirty-seven Wistar rats were divided into five groups: group 1, BDL + peginterferon (n = 8); group 2, BDL (n = 8); group 3, sham + peginterferon (n = 7); group 4, sham (n = 7); and group 5, control group (n = 7). Peginterferon-alpha 2b (50 microgr/kg) or saline (1 mL/kg) was administered intraperitonealy every week for four weeks. Serum biochemical markers, liver tissue oxidative stress, collagen and transforming growth factor-beta (TGF-beta) levels were examined after four weeks. Liver slides were stained by hematoxylin and eosin and Masson trichrome\Gomory reticulum staining.

Results: The levels of tissue collagen, TGF-beta, biochemical markers (AST, ALT, bilirubins, alkaline phosphates, gamma-glutamyl transpeptidase) and oxidative stress markers (Malondialdehyde, luminal, lucigenin) of the BDL group were higher than the sham operated and control groups (all-p < 0.001). Peginterferon improved malondialdehyde, luminal and glutathione levels in the BDL + peginterferon group (p < 0.05). Histopathological examination of the BDL groups showed stage-3 fibrosis, while all the control groups were normal. Peginterferon showed no improvement in fibrosis either histologically, or biochemically.

Conclusions: Peginterferon improved levels of malondialdehyde, glutathione and luminal in the rat model of BDL induced liver fibrosis. Peginterferon however,showed no anti-fibrotic effects in this model and therefore may not be a useful treatment for liver fibrosis.

MeSH terms

  • Animals
  • Bile Ducts
  • Collagen / metabolism
  • Disease Models, Animal
  • Glutathione / metabolism
  • Interferon alpha-2
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use*
  • Ligation
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology*
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / pathology*
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use*
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Transforming Growth Factor beta / metabolism
  • Treatment Outcome

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Polyethylene Glycols
  • Malondialdehyde
  • Collagen
  • peginterferon alfa-2b
  • Glutathione