Experimental model of hepatic fibrosis is importent contributions to the understanding of cellular and molecular mechanisms underlying excessive accumulation of extracellular matrix in the liver. Carbon tetrachloride (Col4) is one of the oldest
and
most
widely used toxin for experimental induction of hepatic fibrosis in laboratory animals.
In this study, we intended to induce the hepatic fibrosis in the rat by the intragastric CCl1/phenobarbital treatment once a week for 12 weeks and the administrationm dosage of CCl4 in each week was determined by the daily body weight change.
Liver
function and histologic change were examined just after 12-wek treatment in group IA (9 rats, phenobarbital treatment only) and II (18 rats, CCI4/phenobarbital treatment). and liver function and the irreversibility of histologic change were
examined 12
weeks after 12-week treatment in group Ib (9 rats, phenobarbital treatment only) and III (18 rats, CCI4/phenobarbital trteatment).
1) Death rate after 12-week treatment was 11% in group 1.56% in group II and 50% in group III. and the highest rate was at 1 week, that is 33% each in group II and III.
2) Total protein, alkaline phosphatase. alanine aminotransferase and portal venous pressure were significantly increased in group II (compared with that in group IA, but it was only portal venous pressure that was increased in group III than in
group
II.
3) The gross finding of micronodular change was shown in 88% of group II, 71% of grou III, but none of group I. The microscopic finding of hepatic fibrosis was found in all of group II and III. but none of group I The severe form of hepatic
fibrosis
suggesting cirrhosis was found in group II and III, 12% and 29% respectively.
In our study, mortality rate was high within 1 week after CCl4 treatment, which resulted in half survival rate after 12-week treatment. We also experienced the low rate of severe fibrotic changes in surviving rats. In the future, in order to
produce a
severe irreversible fibrotic change with low mortality in inducing hepatic fibrosis with CCl4/phenobarbital treatment in the rat, adequate determination of the initial dose of CCl4 and apropriate choice of administration route of CCl4 were
thought
to be
needed.
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