title: Resistance of metallothionein-III null mice to cadmium-induced acute hepatotoxicity.
abstract: We examined the sensitivity of metallothionein (MT)-III null mice to cadmium (Cd)-induced acute hepatotoxicity. MT-I/II null mice were also used to compare Cd toxicities between MT-III null mice and MT-I/II null mice. Male MT-I/II null mice, MT-III null mice and wild-type mice were given s.c. injection of Cd (5-20 micromol/kg) and then the blood and liver were collected from each mouse under ether anesthesia at 2 days after the administration. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities elevated by injection of Cd were significantly higher in the MT-I/II null mice than in the wild-type mice. In the MT-III null mice, ALT and AST activities were not elevated following the injection of Cd. Further, marked morphological changes such as necrosis of hepatocytes, severe hemorrhage and congestion were observed by injection of Cd in both MT-I/II null mice and wild-type mice, whereas the degree of injury was found to be more extensive in MT-I/II null mice. In contrast, only occasional damage was observed in the liver of MT-III null mice treated with the same dose of Cd. These morphological observations were consistent with the results of ALT and AST activities. In the present study, it was clearly found that MT-III null mice were resistant to Cd hepatotoxicity, although MT-I/II null mice were sensitive to its toxicity. MT-III may be an accelerative factor in Cd-induced acute hepatotoxicity.
authors.affiliation: Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, Aichi, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Honda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komuro
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seko
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
authors.forename: Isao
authors.initials: I
authors.lastname: Hozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002104:Cadmium / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D000090023:Metallothionein 3; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D002104:Cadmium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase