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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number4 SUPPL.
Publication statusPublished - 2000 Apr

Fingerprint

Superoxides
Glutathione
Lipopolysaccharides
Liver
Rats
diethyl maleate
Endothelial cells
Endothelial Cells
Purine-Nucleoside Phosphorylase
Glutathione Disulfide
Serum
Alanine Transaminase
Tumor Necrosis Factor-alpha
Body Weight
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge. / Moriya, Susumu; Yokoyama, Hirokazu; Fukuda, Masahiko; Okamura, Yukishige; Kamegaya, Yoshitaka; Mizukami, Takeshi; Ohgo, Hideki; Ishii, Hiromasa.

In: Alcoholism: Clinical and Experimental Research, Vol. 24, No. 4 SUPPL., 04.2000.

Research output: Contribution to journalArticle

Moriya, Susumu ; Yokoyama, Hirokazu ; Fukuda, Masahiko ; Okamura, Yukishige ; Kamegaya, Yoshitaka ; Mizukami, Takeshi ; Ohgo, Hideki ; Ishii, Hiromasa. / Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge. In: Alcoholism: Clinical and Experimental Research. 2000 ; Vol. 24, No. 4 SUPPL.
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abstract = "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.",
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T1 - Glutathione depletion enhances the formation of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge

AU - Moriya, Susumu

AU - Yokoyama, Hirokazu

AU - Fukuda, Masahiko

AU - Okamura, Yukishige

AU - Kamegaya, Yoshitaka

AU - Mizukami, Takeshi

AU - Ohgo, Hideki

AU - Ishii, Hiromasa

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N2 - 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.

AB - 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.

KW - Glutathione Disulfide

KW - Lipopolysaccharide

KW - Reduced Form of Glutathione

KW - Superoxide Anion

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