Alteration of Acetaminophen Metabolism by Sulfate and Steroids in Primary Monolayer Hepatocyte Cultures of Rats and Mice
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概要
- 論文の詳細を見る
Sulfotransferase (ST) is considered to be generally not induced by xenobiotics. However, it has been reported that steroids such as dexamethasone (DEX) and pregnenolone-16α-carbonitrile (PCN) are effective ST inducers in rats, and sulfation of xenobiotics is quite different in rats and mice. The present study is primarily aimed at determining the effect of sulfate and steroids on the metabolism of acetaminophen (AA) in vitro using monolayer cultured hepatocytes of Sprague-Dawley rats and ICR mice Hepatocytes of rats and mice. were incubated with inorganic sulfate (0.25,0.5,1.0,2.0,4.0 mM) and AA in SO_4-depleted media. AA sulfation rates increased as the sulfate concentration was raised to 1.0 mM in rats, whereas the addition of inorganic sulfate to the media had a lesser effect in mice hepatocytes. After pretreatment with DEX (0.1,1.0,10,100 μM) and PCN (0.1,1.0,10 μM) for 3 d, hepatocytes were incubated with AA in media containing 4.0 mM SO^-_4. Pretreatment of the hepatocytes with DEX caused an increase in the glucuronidation and sulfation of AA by 2-3 folds in rats, but to a lesser extent in mice. PCN significantly enhanced the formation of AA-glucuronide and AA-sulfate in mice, but had a minimal effect on rat hepatocytes. In summary, sulfate and DEX markedly enhanced the formation of AA-sulfate in rats hepatocytes, and DEX and PCN increased the sulfation of AA in mice hepatocyte. These results partially support the claim that DEX and PCN are effective ST and uridine diphosphate-glucuronyltransferase inducers in vivo.
- 社団法人日本薬学会の論文
- 1999-03-15
著者
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Kim Hyo
Department of Internal Medicine, Seoul National University College of Medicine, Cardiovascular Labor
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Choung Se
韓国
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Choung Se
College Of Pharmacy Kyung Hee University
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Kim Sung
School Of Dentistry Kyunghee University
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Kim H
Ewha Womans Univ. Seoul Kor
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Choung S
Kyung Hee Univ. Seoul Kor
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SEO Kyung
Department of Toxicology, Korea Food and Drug Administration
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OH Mi
Department of Toxicology, Korea Food and Drug Administration
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Kim H
Chonnam National Univ. Gwangju Kor
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Oh Mi
Department Of Toxicology Korea Food And Drug Administration
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Kim Sung
School Of Computer Science And Engineering Chung-ang University
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Seo Kyung
Dept. Of Toxicology National Institute Of Toxicological Research Korea Food And Drug Administration
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Seo Kyung
Department Of Chmical Techology Seoul National University
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Kim Hyo
Department Of Biological Sciences University Of Ulsan
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Kim Sung
School Of Computer Sci. And Engineering Chung-ang Univ.
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Kim Hyo
Department Of Agro-environmental Sciences Faculty Of Agriculture Kyushu University
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Oh Mi
Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University
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