Cadmium (Cd) is a highly hepatotoxic heavy metal, which is widely dispersed in the environment. Acute Cd
hepatotoxicity has been well studied in experimental animals; however, effects of prolonged exposure to Cd
doses on the liver remain unclear. In the present study, to evaluate chronic Cd hepatotoxicity, we examined
specimens from cases of itai-itai disease, the most severe form of chronic Cd poisoning. We compared 89 cases
of itai-itai disease with 27 control cases to assess Cd concentration in organs. We also examined 80 cases of
itai-itai disease and 70 control cases for histopathological evaluation. In addition, we performed immunohistochemistry
for metallothionein, which binds and detoxifies Cd. Hepatic Cd concentration was higher than
Cd concentration in all other organs measured in the itai-itai disease group, whereas it was second highest
following renal concentration in the control group. In the liver in the itai-itai disease group, fibrosis
was observed at a significantly higher rate than that in the control group. Metallothionein expression was
significantly higher in the itai-itai disease group than that in the control group. Prolonged exposure to low
doses of Cd leads to high hepatic accumulation, which can then cause fibrosis; however, it also causes high
expression of metallothionein, which is thought to reduce Cd hepatotoxicity