Metallothionein-null mice are sensitive to endotoxine/D-galactosamine-induced hepatotoxicity

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.