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

Susumu Moriya, Hirokazu Yokoyama, Masahiko Fukuda, Yukishige Okamura, Yoshitaka Kamegaya, Takeshi Mizukami, Hideki Ohgo, Hiromasa Ishii

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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 α (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.

Original languageEnglish
Pages (from-to)59S-63S
JournalAlcoholism: Clinical and Experimental Research
Issue number4 SUPPL.
Publication statusPublished - 2000 Apr 1



  • Glutathione Disulfide
  • Lipopolysaccharide
  • Reduced Form of Glutathione
  • Superoxide Anion

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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