LOSS OF VIABILITY AFTER DISULFIRAM TREATMENT WITHOUT PRECEDING DEPLETION OF INTRACELLULAR GSH
スポンサーリンク
概要
- 論文の詳細を見る
Effects of disulfiram (DSF) on freshly isolated hepatocytes were examined. Its effects on the cellular reduced form of glutathione (GSH) were triphasic ; GSH decreased instantly after the addition of DSF, teturned to subnormal levels within 30 min, and then declined gradually. The initial decrease in GSH after DSF treatment and the subsequent recovery of GSH were accompanied by an increase and decrease in the oxidized form of gluiathione (GSSG), respectively. Decreases in cell viability brought about by 0.4 mM of DSF were correlated with the later gradual decrease in GSH. The loss of viability by DSF treatment seemed to appear when the intial GSH levels became lower than approximately 5 nmole/10^6 cells. Hepatocyte toxicity of DSF was potentiated by diethylmaleate (GSH depletor) and inhibited by N-acetylcysteine (GSH biosynthesis precursor). 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of GSH reductase, inhibited the GSH recovery and potentiated the toxicity. Respiration of hebatocytes was also inhibited by DSF. Free sulfhydryl groups other than GSH showed similar changes to those of GSH. From these results, it seemed that DSF reacted with cellular GSH and other free sulfhydryl groups to form diethyldithiocarbamate and GSSG, GSSG was feduced back to GSH by glutathione reductase, and the detrease in the viability was dependent on the initial loss of GSH.
- 日本トキシコロジー学会の論文
- 1990-05-25
著者
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Ohe Yuichiro
国立医薬品食品衛生研究所
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Ohe Yuichiro
Department Of Medical Oncology National Cancer Center Hospital
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Ohno Yasuo
National Institute of Health Sciences
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Ohno Yasuo
Div. Of Pharmacology Biological Safty Research Center National Institute Of Hygienic Sciences
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Kawanishi Toru
Div. Of Drugs National Inst. Of Health Sci. Jpn
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Kawanishi T
大妻女子大学 食物学科
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Kawanishi T
Division Of Drugs National Institute Of Health Science
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Kawanishi Toru
National Institute Of Health Sciences
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Hirota Kouichi
Division Of Pharmacology National Institute Of Hygienic Sciences
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Hirota Kouichi
National Institute Of Hygienic Sciences Biological Safety Research Center Division Of Pharmabology
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Takahashi Atsushi
Division Of Pharmacology National Institute Of Hygienic Sciences
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KOBAYASI TADASHI
Kobe Pharmaceutical University
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Kawanishi Toru
Division Of Drugs National Institute Of Health Science
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Kawanishi Toru
国立医薬品食品衛生研究所
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TAKANAKA Akira
The Organization for Pharmaceutical Safety and Research
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Takanaka Akira
Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
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Takanaka A
National Inst. Hygienic Sciences Tokyo Jpn
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Takanaka Akira
National Institute Of Hygienic Sciences
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Kawanishi T
National Institute Of Hygienic Sciences Biological Safety Research Center Division Of Pharmabology
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Ohno Yasuo
National Inst. Of Health Sci. Tokyo Jpn
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Takahashi A
Division Of Pharmacology Bsrc National Institute Of Hygienic Sciences
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