Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge

Citation
S. Moriya et al., Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge, ALC CLIN EX, 24(4), 2000, pp. 59S-63S
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Psycology & Psychiatry","Neurosciences & Behavoir
Journal title
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
ISSN journal
0145-6008 → ACNP
Volume
24
Issue
4
Year of publication
2000
Supplement
S
Pages
59S - 63S
Database
ISI
SICI code
0145-6008(200004)24:4<59S:GDETFO>2.0.ZU;2-J
Abstract
Background: We examined the effects of glutathione depletion on the level o f superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge. 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.