Gamma-glutamylcysteinylethyl ester attenuates progression of carbon tetrachloride-induced acute liver injury in mice.
We examined the effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which is readily transported into hepatocytes and increases hepatocellular reduced glutathione (GSH) levels, on the progression of carbon tetrachloride (CCl4)-induced liver injury in mice in comparison with that of GSH. Administration of more than 160 micromol/kg of gamma-GCE, but not GSH, to mice at 3 h after intraperitoneal injection of CCl4 (1 ml/kg) significantly attenuated increases in serum aspartate aminotransferase and alanine aminotransferase activities at 24 h after the CCl4 injection. Increases in hepatic lipid peroxide (LPO) concentrations and decreases in hepatic GSH concentrations after the CCl4 injection were significantly diminished by the gamma-GCE (160 micromol/kg) administration, but not by the same dose of GSH. Gamma-GCE, gamma-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 gamma-GCE attenuates the progression of CCl4-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 gamma-GCE in the liver cells.
Nishida
K
K
Department of Biochemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan. knishida@fujita-hu.ac.jp
Ohta
Y
Y
Ishiguro
I
I
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D004151:Dipeptides / Q000627:therapeutic use*; D005978:Glutathione / Q000627:therapeutic use; D008107:Liver Diseases / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D051379:Mice
D004151:Dipeptides; C067744:N-gamma-glutamylcysteine ethyl ester; D002251:Carbon Tetrachloride; D005978:Glutathione