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/
H. Okabe et al., 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/, Circulatory shock, 41(4), 1993, pp. 268-272
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.