2001 年 24 巻 7 号 p. 749-753
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.
