Role of renal gamma-glutamyltransferase activity in hepatic utilization of exogenous glutathione.

The importance of renal gamma-glutamyltransferase activity in the hepatic utilization of exogenous glutathione (GSH) was evaluated by injecting GSH (1.67 mmol/kg body wt) i.v. into bilaterally nephrectomized and sham-operated Sprague-Dawley rats in which endogenous hepatic GSH had been decreased (0.20 +/- 0.01 mumol/g liver vs 5.87 +/- 0.26 mumol/g liver in normal controls, mean +/- SD) by diethylmaleate (0.5 ml/kg body wt, i.p.). Hepatic GSH concentration 60 min after GSH administration was lower in the nephrectomized than in the sham-operated rats (0.87 +/- 0.25 mumol/g liver vs 3.08 +/- 0.81 mumol/g liver, P < 0.001), while plasma GSH concentration was higher in the former (4.61 +/- 1.07 mM vs 0.11 +/- 0.06 mM, P < 0.001). In rats with intact kidneys which had been given a gamma-glutamyltransferase inhibitor (acivicin, 25 mumol/kg body wt i.v.) prior to GSH administration, the hepatic GSH concentrations (1.11 +/- 0.49 mumol/g liver) were comparable to those obtained in the nephrectomized rats. When N-acetylcysteine (1.67 mmol/kg body wt, i.v.) was administered instead of GSH, the hepatic GSH concentrations were similar in nephrectomized and sham-operated rats (1.54 +/- 0.23 mumol/g liver vs 2.22 +/- 0.58 mumol/g liver, NS). The gamma-glutamyltransferase activity was much higher in the kidney than in the liver (4460 +/- 830 IU/kg body wt vs 14 +/- 7 IU/kg body wt). These results indicate that the kidney plays an essential role in the hepatic utilization of exogenous GSH through its high gamma-glutamyltransferase activity.