Mechanism of Protection by S-(1,2-Dicarboxyethyl) glutathione Triester against Acetaminophen-Induced Hepatotoxicity in Rat Hepatocytes.
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- YASUDA Makoto
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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- MATSUMOTO Shuji
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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- MATSUSHIMA Satoshi
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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- MURATA Hiroko
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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- SHIMOSHINBARA Tsunashi
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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- TSUBOI Seiji
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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Treatment with the triester of S-(1,2-dicarboxyethyl)glutathione (DCE-GS) prevented the hepatotoxicity induced by acetaminophen via elevation of the glutathione (GSH) level in rat hepatocytes. This elevation of the GSH level in rat hepatocytes by DCE-GS triester was dose- and time-dependent (2.1-fold in 24 h with 0.5 mM). DCE-GS triester increased the GSH level much more effectively than GSH, DCE-GS, and DCE-GS monoester and diester. Furthermore, the activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme in GSH biosynthesis, was also increased by DCE-GS triester treatment (1.4-fold in 24 h with 1.0 mM). In contrast, with a rat liver homogenate, DCE-GS increased the γ-GCS activity, whereas DCE-GS triester had no effect on this activity. These results suggested that DCE-GS triester, which is transported into hepatocytes much more effectively than DCE-GS and other DCE-GS esters due to its greater lipophilicity, was hydrolyzed to DCE-GS, and then the DCE-GS produced increased the GSH level via activation of γ-GCS in rat hepatocytes.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 24 (7), 749-753, 2001
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679603868672
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- NII論文ID
- 110003638555
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3MXkvVaru7w%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 5820729
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- PubMed
- 11456112
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可