title: The liver in itai-itai disease (chronic cadmium poisoning): pathological features and metallothionein expression.
abstract: 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.
authors.affiliation: Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Baba
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Megumi
authors.initials: M
authors.lastname: Yazaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Nagata
authors.forename: Takashi
authors.initials: T
authors.lastname: Minamisaka
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Tsuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hayashi
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Miwa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakajima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Keiko
authors.initials: K
authors.lastname: Aoshima
authors.forename: Johji
authors.initials: J
authors.lastname: Imura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D002104:Cadmium / Q000009:adverse effects* / Q000032:analysis; D002105:Cadmium Poisoning / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000175:diagnosis; D008668:Metallothionein / Q000032:analysis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D015854:Up-Regulation
chemical_list: D004785:Environmental Pollutants; D002104:Cadmium; D008668:Metallothionein