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J.Health Sci., 47(3), 310-313, 2001
Metallothionein-Null Mice Are Sensitive to Endotoxine/D-Galactosamine-Induced Hepatotoxicity
Tomoki Kimura,a Takatoshi Koujitani,b Norio Itoh,*, a Miyako Takehara,a Ikuyo Oguro,a Jun-ichi Ishizaki,a Tsuyoshi Nakanishi,a and Keiichi Tanakaa
aDepartment of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan and bDepartment of Toxicology and Teratology, Developmental Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka 564-0053, Japan
Metallothionein (MT), which is a low-molecular weight, cysteine-rich, metal-binding protein, is induced during acute-phase reactions. However, the specific function of MT in the acute-phase response remains to be elucidated. We previously reported that MT-I, II deficient (MT-null) mice are highly sensitive to the lethal effects of lipopolysaccharide (LPS)/D-galactosamine (GalN). We designed the present study to clarify the major cause of the differences in the sensitivity to the lethal effects of LPS/GalN between wild type and MT-null mice. We found that histological grade of hepatocellular necrosis, induced by LPS/GalN, was greater in MT-null mice than in wild type mice. Therefore, the present findings suggest that MT induction has the potential as an attenuator of LPS/GalN-induced liver necrosis.
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