A Protective Role for Metallothionein in Acetaminophen-caused Liver Toxicity via Oxidative Stress(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)

概要

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To investigate the possible involvement of metallothionein (MT) in acetaminophen (AC)-induced liver damage, MT-I and MT-II gene knock-out transgenic mice (MT-null mice) and wild-type control mice were i.p. treated with AC at a single dose of 250mg/kg and compared. At 24h after AC treatment severe liver damage characterized by necrosis of hepatocytes and increased serum GPT activity was found in MT-null mice while a limited degree of change such as a slight increase in serum GPT activity without necrosis was observed in wild-type mouse liver. MT-null hepatocytes also showed elevated PCNA (proliferating cell nuclear antigen)-positive activity around the necrosis area. AC administration resulted in an increase in lipid peroxidation in MT-null mice, but not in the wild-type mice. The liver in the wild-type mice showed an increased MT amount after AC treatment. These results indicate that MT acts as an endogenous defensive factor against AC-induced hepatotoxicity via oxidative stress.
公益社団法人日本薬学会の論文
1999-02-28