Site-Specific Induction of Metallothionein in N-Nitrosodimethylamine-Treated Rat Liver
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概要
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The effects of dietary protein and sulfur-containing amino acids on oxidative responses against N-nitrosodimethylamine (NDMA) treatment were investigated in rat liver, focusing on the mechanism of metallothionein (MT) induction. Rats were fed a 10% soybean protein isolate (SPI) diet or SPI supplemented with 0.3% L-methionine (SPI-Met) for 3 weeks after weaning. Rats fed on SPI showed lower glutathione (GSH) levels and higher MT levels in the liver than those fed on SPI-Met. After treatment with NDMA (20 mg/kg, i.p.), MT levels were elevated significantly in both groups, whereas GSH levels were only elevated in the SPI group. Pathologically, necrosis and hemorrhage were seen in the livers of NDMA-treated rats of both dietary groups, suggesting oxidative damage caused by NDMA treatment. Immunological histochemistry using anti-MT antibody showed that most of the MT was distributed in the cytosol region of all the rat groups. The ratios of the MT-positive cells were correlated to MT levels that were chemically analyzed. It was notable that the localization of MT staining in the hepatic lobules was altered after NDMA injection. The MT staining was principally observed around the central vein before injection, whereas it was more markedly observed at the peripheral region after NDMA treatment. These results indicate that the synthesis of hepatic MT basically occurs around the central vein with oxygen stress caused by insufficient oxygen supplement and/or stimulated oxygen consumption. NDMA could be oxidatively metabolized at the peripheral region with sufficient supplemental oxygen from the artery, resulting in oxidative stress and stimulation of MT synthesis there. Thus, distribution of tissue MT might vary depending on the site of oxidative stress.
- 公益社団法人日本薬学会の論文
- 2003-04-01
著者
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Yasutake Akira
Biochemistry Section Department Of Basic Medical Sciences National Institute For Minamata Disease
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Yasutake Akira
Biochemistry Section National Institute For Minamata Disease
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Mizutani Yusuke
Department Of Veterinary Pathology Tottori University
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Shimada Akinori
Department Of Comparative Pathology Faculty Of Veterinary Medicine Hokkaido University
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Taniguchi Misako
Division Of Food And Nutrition Nakamura Gakuen University
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Shimada Akinori
Department of Veterinary Pathology,Tottori University
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