Resistance of metallothionein-III null mice to cadmium-induced acute hepatotoxicity

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  • Honda Akiko
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University
  • Komuro Hiroaki
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University
  • Hasegawa Tatsuya
    Department of Environmental Biochemistry, Yamanashi Institute of Environmental Sciences
  • Seko Yoshiyuki
    Department of Environmental Biochemistry, Yamanashi Institute of Environmental Sciences
  • Shimada Akinori
    Department of Veterinary Pathology, Faculty of Agriculture, Tottori University
  • Nagase Hisamitsu
    Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University
  • Hozumi Isao
    Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine
  • Inuzuka Takashi
    Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine
  • Hara Hideaki
    Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University
  • Fujiwara Yasuyuki
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University
  • Satoh Masahiko
    Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University

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  • Resistance of metallothionein-3 null mice to cadmium-induced acute hepatotoxicity
  • Resistance of metallothionein-null mice to cadmium-induced acute hepatotoxicity

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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 µmol/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.

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