1. The aim of the present study was to develop an experimental model of liv
er cirrhosis in rabbits using CCl4 and phenobarbital.
2. Liver cirrhosis was induced in male New Zealand white rabbits (n = 10) b
y intragastric administration of CCl4 once weekly starting 14 days after th
e addition of phenobarbital to the drinking water (50 mg/day). Controls rec
eived phenobarbital only (n = 7). Alanine aminotransferase (ALT), aspartate
aminotransferase (AST), gamma -glutamyl transpeptidase (GGT), albumin and
bilirubin levels were determined throughout CCl4 treatment. The initial dos
e of CCl4 was 20 mug and subsequent doses were calculated to maintain AST a
nd ALT levels between 400 and 800 IU/L for the duration of treatment (16 we
eks). Indocyanine green (ICG) clearance was performed before and at the end
of CCl4 treatment. Animals were killed at 16 weeks and three fragments of
each liver lobe were processed for histological examination. A semiquantita
tive score was used to evaluate the development of fibrosis.
3. Cirrhosis developed in 80% of rabbits treated with CCl4. These animals d
id not gain weight compared with controls (P < 0.05). A significant reducti
on of ICG clearance was observed in CCl4-treated rabbits compared with cont
rols (P < 0.05). The AST, ALT, bilirubin and gamma -GGT levels were elevate
d in CCl4-treated rabbits.
4. In conclusion, this model is successful in producing liver cirrhosis and
may be useful in studies investigating metabolic, immunological or biochem
ical changes during the evolution of chronic liver disease.