INCREASE IN THE PLASMA-CONCENTRATION OF REDUCED GLUTATHIONE OBSERVED IN RATS WITH LIVER-DAMAGE INDUCED BY LIPOPOLYSACCHARIDE D-GALACTOSAMINE - EFFECTS OF ULINASTATIN, A URINARY TRYPSIN-INHIBITOR/

The changes in plasma concentrations of reduced glutathione were inves tigated in rats with endotoxin hepatitis. An increase in serum alanine aminotransferase activity and in serum total bilirubin concentration was observed 12 hr after the intraperitoneal co-administration of smal l doses of Escherichia coil lipopolysaccharide and D-galactosamine in starved rats. At the same time, an increase in the plasma concentratio n of reduced glutathione was also observed. The increase in reduced gl utathione from 14 +/- 2 to 20 +/- 9 mu M (n = 11, P < 0.05) correlated well with that in serum alanine aminotransferase activity. Ulinastati n, a potent inhibitor of polymorphonuclear leukocyte elastase, partial ly counteracted all of these changes. Ulinastatin also reduced histolo gical liver damage induced by endotoxin. We conclude that the increase in the plasma concentration of reduced glutathione reflects hepatocel lular damage associated with endotoxin hepatitis. The partial reversal of the damage by ulinastatin is consistent with the proposal that the activation of polymorphonuclear leukocytes is involved in endotoxin h epatitis, (C) 1993 Wiley-Liss, Inc.