Preventive effect of gamma-glutamylcysteinylethyl ester on immunological cell injury in isolated rat hepatocytes with anti-rat liver plasma membrane antiserum treatment.

We studied the mechanism by which gamma-glutamylcysteinylethyl ester (gamma-GCE), which is rapidly transported into hepatocytes and converted to reduced glutathione (GSH), prevents immunological hepatic injury. The effect of gamma-GCE on cell injury, as estimated by release of transaminases from cells, and changes in phospholipase A2 (PLA2) activity and of GSH, Ca2+, and lipid peroxide (LPO) contents were examined in isolated rat hepatocytes treated with anti-rat liver plasma membrane rabbit antiserum (ALPMA) and compared with that of GSH. gamma-GCE prevented not only the release of transaminases from hepatocytes treated with ALPMA but also a decrease in GSH content, activation of PLA2, and increases in Ca2+ and LPO contents in the damaged hepatocytes. However, the preventive effect of GSH on these changes was weaker than that of gamma-GCE. In addition, gamma-GCE prevented the development of cell injury in ALPMA-pretreated hepatocytes. These results suggest that gamma-GCE prevents immunological cell injury in ALPMA-treated rat hepatocytes mainly by maintaining the integrity of the plasma membrane through its conversion to GSH within the cells.