A unique rat model of bile ductular hyperplasia in which liver is almost totally replaced with well-differentiated bile ductules.

A novel rat model was developed in which furan combined in a unique synergistic manner with bile duct ligation to induce replacement of most of liver with well-differentiated hyperplastic bile ductules. Multiple tissue sections of liver from Fischer 344 male rats first subjected to a bile duct ligation and 1 week later given furan by gavage at 45 mg/kg body weight, once a day, five times weekly for 5 to 6 weeks, exhibited a mean percent of bile ductule tissue per total liver section area of 72.6 +/- 16.3% compared to control values of 20.0 +/- 4.2% for bile duct-ligated rats that received corn oil by gavage instead of furan and 11.9 +/- 3.1% for rats that were given a sham operation followed by furan. This dramatic difference was also reflected by the very high mean gamma-glutamyl transpeptidase specific activity of liver homogenates from the bile duct-ligated/furan-treated rats, which was approximately 8 x 10(3) nmoles p-nitroaniline/mg protein/hour versus values of approximately 2 x 10(3) for bile duct-ligated/corn oil control, approximately 1 x 10(3) for sham-operated/furan-treated control, and 44.9 for untreated rat. The data presented support a potentially powerful experimental model for investigating bile ductular cell functions, differentiation, and proliferation.