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Development Of An Experimental Model Of Liver Cirrhosis In Rabbits
Author(s) -
Brandão CG,
Ferreira HHA,
Piovesana H,
Polimeno NC,
Ferraz JGP,
De Nucci G,
Pedrazzoli J
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03381.x
Subject(s) - cirrhosis , ccl4 , phenobarbital , bilirubin , medicine , indocyanine green , albumin , carbon tetrachloride , endocrinology , gastroenterology , pathology , chemistry , organic chemistry
SUMMARY 1. The aim of the present study was to develop an experimental model of liver cirrhosis in rabbits using CCl 4 and phenobarbital. 2. Liver cirrhosis was induced in male New Zealand white rabbits ( n = 10) by intragastric administration of CCl 4 once weekly starting 14 days after the addition of phenobarbital to the drinking water (50 mg/day). Controls received phenobarbital only ( n = 7). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ ‐glutamyl transpeptidase (GGT), albumin and bilirubin levels were determined throughout CCl 4 treatment. The initial dose of CCl 4 was 20 μ g and subsequent doses were calculated to maintain AST and ALT levels between 400 and 800 IU/L for the duration of treatment (16 weeks). Indocyanine green (ICG) clearance was performed before and at the end of CCl 4 treatment. Animals were killed at 16 weeks and three fragments of each liver lobe were processed for histological examination. A semiquantitative score was used to evaluate the development of fibrosis. 3. Cirrhosis developed in 80% of rabbits treated with CCl 4 . These animals did not gain weight compared with controls ( P < 0.05). A significant reduction of ICG clearance was observed in CCl 4 ‐treated rabbits compared with controls ( P < 0.05). The AST, ALT, bilirubin and γ ‐GGT levels were elevated in CCl 4 ‐treated rabbits. 4. In conclusion, this model is successful in producing liver cirrhosis and may be useful in studies investigating metabolic, immunological or biochemical changes during the evolution of chronic liver disease.