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.
Tamano
T
T
Second Department of Internal Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Yoshida
H
H
Kuronuma
Y
Y
Harada
T
T
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D005978:Glutathione / Q000008:administration & dosage / Q000378:metabolism*; D007275:Injections, Intravenous; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*
D007555:Isoxazoles; D008298:Maleates; D005723:gamma-Glutamyltransferase; C014476:diethyl maleate; D005978:Glutathione; C006303:acivicin; D000111:Acetylcysteine