The liver in itai-itai disease (chronic cadmium poisoning): pathological features and metallothionein expression

• DOI: 10.1038/modpathol.2013.62
• Publication Date: 2013-04-05T11:42:46Z
• Authors: Hayato Baba; Koichi Tsuneyama; Megumi Yazaki; Kohei Nagata; Takashi Minamisaka; Tatsuhiro Tsuda; Kazuhiro Nomoto; Shinichi Hayashi; Shigeharu Miwa; Takahiko Nakajima; Yuko Nakanishi; Keiko Aoshima; Johji Imura
• Keywords: Aged, 80 and over; Liver Cirrhosis; Cadmium Poisoning; 0303 health sciences; Chi-Square Distribution; Middle Aged; Immunohistochemistry; Up-Regulation; 3. Good health; 03 medical and health sciences; Liver; Predictive Value of Tests; Case-Control Studies; Chemical and Drug Induced Liver Injury, Chronic; Humans; Environmental Pollutants; Female; Metallothionein; Autopsy; Aged; Cadmium

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.