γ-Glutamylcysteinylethyl ester attenuates progression of carbon tetrachloride-induced acute liver injury in mice

Abstract

We examined the effect of γ-glutamylcysteinylethyl ester ( γ-GCE), which is readily transported into hepatocytes and increases hepatocellular reduced glutathione (GSH) levels, on the progression of carbon tetrachloride (CCl 4)-induced liver injury in mice in comparison with that of GSH. Administration of more than 160 μmol/kg of γ-GCE, but not GSH, to mice at 3 h after intraperitoneal injection of CCl 4 (1 ml/kg) significantly attenuated increases in serum asparatate aminotransferase and alanine aminotransferase activities at 24 h after the CCl 4 injection. Increases in hepatic lipid peroxide (LPO) concentrations and decreases in hepatic GSH concentrations after the CCl 4 injection were significantly diminished by the γ-GCE (160 μmol/kg) administration, but not by the same dose of GSH. γ-GCE, γ-glutamylcysteine, and cysteine acted as substrates for glutathione peroxidases much less efficiently than GSH in the post-mitochondrial fraction of normal mouse liver cells. These results indicate that γ-GCE attenuates the progression of CCl 4-induced acute liver injury in mice through the maintenance of hepatic GSH levels, leading to inhibition of hepatic LPO formation, which could be due to an efficient utilization of GSH converted from γ-GCE in the liver cells.