Ae. Sirica et al., A UNIQUE RAT MODEL OF BILE DUCTULAR HYPERPLASIA IN WHICH LIVER IS ALMOST TOTALLY REPLACED WITH WELL-DIFFERENTIATED BILE DUCTULES, The American journal of pathology, 144(6), 1994, pp. 1257-1268
A novel rat model was developed in which furan combined in a unique sy
nergistic manner with bile duct ligation to induce replacement of most
of liver with well-differentiated hyperplastic bile ductules. Multipl
e 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 m
g/kg body weight, once a day, five times weekly for 5 to 6 weeks, exhi
bited a mean percent of bile ductule tissue per total liver section ar
ea of 72.6 +/- 16.3% compared to control values of 20.0 +/- 4.2% for b
ile duct-ligated rats that received corn oil by gavage instead of fura
n 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 hig
h mean gamma-glutamyl transpeptidase specific activity of liver homoge
nates from the bile duct-ligated/furan-treated rats, which was similar
to 8 x 10(3) nmoles p-nitroaniline/ mg protein/hour versus values of
similar to 2 x 10(3) for bile duct-ligated/corn oil control, similar t
o 1 x 10(3) for sham-operated/furan-treated control, and 44.9 for untr
eated rat. The data presented support a potentially powerful experimen
tal model for investigating bile ductular cell functions, differentiat
ion, and proliferation.