Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge

Takeshi Mizukami, Hirokazu Yokoyama, Yukishige Okamura, Hideki Ohgo, Masahiko Fukuda, Yoshitaka Kamegaya, Shinzo Kato, Hiromasa Ishii

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background/Aims: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subsequent damage to endothelial cells of the hepatic sinusoids after lipopolysaccharide challenge. Methods: Rats were given 2 mg/kg body weight lipopolysaccharide. Three hours after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Damage to endothelial cells of the hepatic sinusoids was assessed from the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the fiver perfusate. To further characterize the mechanisms behind these changes, these studies were done in rats given superoxide dismutase or an anti-TNFα antibody. To study whether the spleen plays a role in the mechanisms, experiments with splenectomized rats were performed. Results: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic sinusoids. These changes were significantly attenuated by the treatments with superoxide dismutase or an antibody against TNFα, as well as by splenectomy. The hepatic macrophage and Kupffer cell populations after lipopolysaccharide challenge were significantly smaller in the rats given splenectomy than in those given a sham operation. There were no significant differences in the neutrophil populations between the two groups. Levels of TNFα were significantly lower in the former than the latter, whereas there were no significant differences in levels of Interleukin-8 between the two groups. Conclusions: Splenectomy reduced the superoxide anion release into the hepatic sinusoids caused by the lipopolysaccharide challenge and subsequent damage to endothelial cells of the hepatic sinusoids. This supports the view that splenectomy has a protective effect in lipopolysaccharide-induced liver injury.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalJournal of Hepatology
Volume31
Issue number2
DOIs
Publication statusPublished - 1999 Aug
Externally publishedYes

Fingerprint

Splenectomy
Superoxides
Lipopolysaccharides
Liver
Endothelial Cells
Superoxide Dismutase
Spleen
Purine-Nucleoside Phosphorylase
Kupffer Cells
Cytochromes
Alanine Transaminase
Interleukin-8
Population
Anti-Idiotypic Antibodies
Hepatocytes
Neutrophils
Perfusion
Macrophages
Body Weight
Antibodies

Keywords

  • Cytochrome C
  • Hepatic macrophages
  • Kupffer cells
  • Lipopolysaccharide
  • Splenectomy
  • Superoxide anion

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge. / Mizukami, Takeshi; Yokoyama, Hirokazu; Okamura, Yukishige; Ohgo, Hideki; Fukuda, Masahiko; Kamegaya, Yoshitaka; Kato, Shinzo; Ishii, Hiromasa.

In: Journal of Hepatology, Vol. 31, No. 2, 08.1999, p. 235-241.

Research output: Contribution to journalArticle

Mizukami, Takeshi ; Yokoyama, Hirokazu ; Okamura, Yukishige ; Ohgo, Hideki ; Fukuda, Masahiko ; Kamegaya, Yoshitaka ; Kato, Shinzo ; Ishii, Hiromasa. / Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge. In: Journal of Hepatology. 1999 ; Vol. 31, No. 2. pp. 235-241.
@article{c506e77c07204bee946d3b3e57626d42,
title = "Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge",
abstract = "Background/Aims: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subsequent damage to endothelial cells of the hepatic sinusoids after lipopolysaccharide challenge. Methods: Rats were given 2 mg/kg body weight lipopolysaccharide. Three hours after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Damage to endothelial cells of the hepatic sinusoids was assessed from the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the fiver perfusate. To further characterize the mechanisms behind these changes, these studies were done in rats given superoxide dismutase or an anti-TNFα antibody. To study whether the spleen plays a role in the mechanisms, experiments with splenectomized rats were performed. Results: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic sinusoids. These changes were significantly attenuated by the treatments with superoxide dismutase or an antibody against TNFα, as well as by splenectomy. The hepatic macrophage and Kupffer cell populations after lipopolysaccharide challenge were significantly smaller in the rats given splenectomy than in those given a sham operation. There were no significant differences in the neutrophil populations between the two groups. Levels of TNFα were significantly lower in the former than the latter, whereas there were no significant differences in levels of Interleukin-8 between the two groups. Conclusions: Splenectomy reduced the superoxide anion release into the hepatic sinusoids caused by the lipopolysaccharide challenge and subsequent damage to endothelial cells of the hepatic sinusoids. This supports the view that splenectomy has a protective effect in lipopolysaccharide-induced liver injury.",
keywords = "Cytochrome C, Hepatic macrophages, Kupffer cells, Lipopolysaccharide, Splenectomy, Superoxide anion",
author = "Takeshi Mizukami and Hirokazu Yokoyama and Yukishige Okamura and Hideki Ohgo and Masahiko Fukuda and Yoshitaka Kamegaya and Shinzo Kato and Hiromasa Ishii",
year = "1999",
month = "8",
doi = "10.1016/S0168-8278(99)80219-0",
language = "English",
volume = "31",
pages = "235--241",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Splenectomy attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide challenge

AU - Mizukami, Takeshi

AU - Yokoyama, Hirokazu

AU - Okamura, Yukishige

AU - Ohgo, Hideki

AU - Fukuda, Masahiko

AU - Kamegaya, Yoshitaka

AU - Kato, Shinzo

AU - Ishii, Hiromasa

PY - 1999/8

Y1 - 1999/8

N2 - Background/Aims: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subsequent damage to endothelial cells of the hepatic sinusoids after lipopolysaccharide challenge. Methods: Rats were given 2 mg/kg body weight lipopolysaccharide. Three hours after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Damage to endothelial cells of the hepatic sinusoids was assessed from the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the fiver perfusate. To further characterize the mechanisms behind these changes, these studies were done in rats given superoxide dismutase or an anti-TNFα antibody. To study whether the spleen plays a role in the mechanisms, experiments with splenectomized rats were performed. Results: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic sinusoids. These changes were significantly attenuated by the treatments with superoxide dismutase or an antibody against TNFα, as well as by splenectomy. The hepatic macrophage and Kupffer cell populations after lipopolysaccharide challenge were significantly smaller in the rats given splenectomy than in those given a sham operation. There were no significant differences in the neutrophil populations between the two groups. Levels of TNFα were significantly lower in the former than the latter, whereas there were no significant differences in levels of Interleukin-8 between the two groups. Conclusions: Splenectomy reduced the superoxide anion release into the hepatic sinusoids caused by the lipopolysaccharide challenge and subsequent damage to endothelial cells of the hepatic sinusoids. This supports the view that splenectomy has a protective effect in lipopolysaccharide-induced liver injury.

AB - Background/Aims: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subsequent damage to endothelial cells of the hepatic sinusoids after lipopolysaccharide challenge. Methods: Rats were given 2 mg/kg body weight lipopolysaccharide. Three hours after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Damage to endothelial cells of the hepatic sinusoids was assessed from the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the fiver perfusate. To further characterize the mechanisms behind these changes, these studies were done in rats given superoxide dismutase or an anti-TNFα antibody. To study whether the spleen plays a role in the mechanisms, experiments with splenectomized rats were performed. Results: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic sinusoids. These changes were significantly attenuated by the treatments with superoxide dismutase or an antibody against TNFα, as well as by splenectomy. The hepatic macrophage and Kupffer cell populations after lipopolysaccharide challenge were significantly smaller in the rats given splenectomy than in those given a sham operation. There were no significant differences in the neutrophil populations between the two groups. Levels of TNFα were significantly lower in the former than the latter, whereas there were no significant differences in levels of Interleukin-8 between the two groups. Conclusions: Splenectomy reduced the superoxide anion release into the hepatic sinusoids caused by the lipopolysaccharide challenge and subsequent damage to endothelial cells of the hepatic sinusoids. This supports the view that splenectomy has a protective effect in lipopolysaccharide-induced liver injury.

KW - Cytochrome C

KW - Hepatic macrophages

KW - Kupffer cells

KW - Lipopolysaccharide

KW - Splenectomy

KW - Superoxide anion

UR - http://www.scopus.com/inward/record.url?scp=0032787824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032787824&partnerID=8YFLogxK

U2 - 10.1016/S0168-8278(99)80219-0

DO - 10.1016/S0168-8278(99)80219-0

M3 - Article

C2 - 10453935

AN - SCOPUS:0032787824

VL - 31

SP - 235

EP - 241

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 2

ER -