Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge.
BACKGROUND
We examined the effects of glutathione depletion on the level of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge.


METHODS
Rats were given 1 mg/kg of maleic acid diethyl ester to deplete glutathione in vivo and then 0.5 mg/kg body weight of lipopolysaccharide.


RESULTS
This treatment significantly depleted serum reduced glutathione (32.7 +/- 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 superoxide 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 glutathione depletion (0.28 +/- 0.04 o.d., p < 0.05). There were no significant differences 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 nondepleted 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-depleted rats than in the nondepleted rats.


CONCLUSIONS
The reduced form of glutathione can decrease levels of the superoxide anion released into hepatic sinusoids and can decrease subsequent damage to endothelial cells in these sinusoids caused by lipopolysaccharide; that is, it can reduce lipopolysaccharide-induced liver injury.
Moriya
S
S
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Yokoyama
H
H
Fukuda
M
M
Okamura
Y
Y
Kamegaya
Y
Y
Mizukami
T
T
Ohgo
H
H
Ishii
H
H
D000818:Animals; D000838:Anions; D005978:Glutathione / Q000097:blood*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000838:Anions; D008070:Lipopolysaccharides; D008298:Maleates; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C014476:diethyl maleate; D005978:Glutathione