Role of renal γ-glutamyltransferase activity in hepatic utilization of exogenous glutathione

The importance of renal γ-glutamyltransferase activity in the hepatic utilization of exogenous glutathione (GSH) was evaluated by injecting GSH (1.67mmol/kg body wt) i.v. into bilaterally nephrectomized and sham-operated Sprague-Dawley rats in which endogenous hepatic GSH had been decreased (0.20±0.01μmol/g liver vs 5.87±0.26μmol/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 ±0.25μol/g liver vs 3.08±0.81μmol/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 γ-glutamyltransferase inhibitor (acivicin, 25 (μmol/kg body wt i.v.) prior to GSH administration, the hepatic GSH concentrations (1.11±0.49μmol/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±0.23μmol/g liver vs 2.22±0.58μmol/g liver, NS). The γ-glutamyltransferase activity was much higher in the kidney than in the liver (4460±830IU/kg body wt vs 14±7IU/kg body wt). These results indicate that the kidney plays an essential role in the hepatic utilization of exogenous GSH through its high γ-glutamyltransferase activity.