This study was undertaken in order to investigate the effect of zinc (Zn) a
dministration on induction of Zn-binding metallothionein in rat liver with
thioacetamide-induced cirrhosis, and the localization of metallothionein in
the liver. Normal and cirrhotic rats received intraperitoneal injections w
ith or without Zn. Subsequently, metal analyses, purification of metallothi
onein by gel filtration and immunohistochemical assessments of metallothion
ein were carried out. Although in Zn-injected cirrhotic rats, the Zn conten
ts in the liver and plasma increased significantly depending upon the dose
of Zn, the Zn contents in the liver and plasma of the cirrhotic rats were l
ower than those of normal rats after the same dose of Zn. The results of ge
l filtration also showed that the levels of Zn-metallothionein in the cirrh
otic liver were reduced in comparison with those of the normal liver. By th
e immunohistochemical method, the presence of metallothionein in the parenc
hymal areas but not in the fibrotic areas of the cirrhotic liver was confir
med. These results suggested that the induced metallothionein was only loca
ted in the parenchymal areas. The metallothionein induced in the parenchyma
l areas was considered to play a role in protecting the parenchymal cells a
gainst the progression of fibrosis, because metallothionein has been though
t to be involved in the cellular defense against oxidative stress.