Background: We examined the effects of glutathione depletion on the level o
f superoxide anion released into hepatic sinusoids after lipopolysaccharide
Methods: Rats were given 1 mg/kg of maleic acid diethyl ester to deplete gl
utathione in vivo and then 0.5 mg/kg body weight of lipopolysaccharide.
Results: This treatment significantly depleted serum reduced glutathione (3
2.7 +/- 1.7 vs. 23.0 +/- 3.2 mM, p = 0.002). However, it did not affect the
serum oxidized glutathione concentration (2.88 +/- 0.56 vs. 3.10 +/- 0.78
mM, not significant). The lipopolysaccharide challenge caused significant s
uperoxide anion formation as compared with controls (0.12 +/- 0.04 vs. 0.22
+/- 0.05 o.d., p < 0.001), and it was enhanced significantly by glutathion
e depletion (0.28 +/- 0.04 o.d., p < 0.05). There were no significant diffe
rences in levels of lipopolysaccharide (2142 +/- 452 vs. 2503 +/- 612 pg/ml
) and tumor necrosis factor alpha (277 +/- 186 vs. 252 +/- 88 pg/ml) after
the lipopolysaccharide challenge between the glutathione-depleted and nonde
pleted rats. Moreover, the purine nucleoside phosphorylase/glutamic-pyruvic
transaminase ratio in liver perfusates, a marker of damage to endothelial
cells in hepatic sinusoids, was significantly higher in the glutathione-dep
leted rats than in the nondepleted rats.
Conclusions: The reduced form of glutathione can decrease levels of the sup
eroxide anion released into hepatic sinusoids and can decrease subsequent d
amage to endothelial cells in these sinusoids caused by lipopolysaccharide;
that is, it can reduce lipopolysaccharide-induced liver injury.