Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome e method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 ± 0.01 vs. 0.12 ± 0.02 o.d., p < 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 ± 0.002 vs. 0.008 ± 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell-depleted rats, compared with the controls (0.14 ± 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 ± 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol-induced liver injury.

Original languageEnglish
JournalAlcoholism: Clinical and Experimental Research
Volume23
Issue number4 SUPPL.
Publication statusPublished - 1999 Apr

Fingerprint

Kupffer Cells
Superoxides
Ethanol
Liver
Endothelial cells
Purine-Nucleoside Phosphorylase
Rats
Alanine Transaminase
Endothelial Cells
Macrophages
Body Weight
Cytochromes
Tumor Necrosis Factor-alpha
Cells
Hepatocytes
Leukocytes
Perfusion

Keywords

  • Cytochrome C
  • Ethanol
  • Hepatic Sinusoidal Endothelial Cell
  • Kupffer Cells
  • Superoxide Anion

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion. / Yokoyama, Hirokazu; Fukuda, Masahiko; Okamura, Yukishige; Mizukami, Takeshi; Ohgo, Hideki; Kamegaya, Yoshitaka; Kato, Shinzo; Ishii, Hiromasa.

In: Alcoholism: Clinical and Experimental Research, Vol. 23, No. 4 SUPPL., 04.1999.

Research output: Contribution to journalArticle

Yokoyama, Hirokazu ; Fukuda, Masahiko ; Okamura, Yukishige ; Mizukami, Takeshi ; Ohgo, Hideki ; Kamegaya, Yoshitaka ; Kato, Shinzo ; Ishii, Hiromasa. / Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion. In: Alcoholism: Clinical and Experimental Research. 1999 ; Vol. 23, No. 4 SUPPL.
@article{b1b192ac018947959ccc81b7dbc404aa,
title = "Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion",
abstract = "Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome e method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 ± 0.01 vs. 0.12 ± 0.02 o.d., p < 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 ± 0.002 vs. 0.008 ± 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell-depleted rats, compared with the controls (0.14 ± 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 ± 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol-induced liver injury.",
keywords = "Cytochrome C, Ethanol, Hepatic Sinusoidal Endothelial Cell, Kupffer Cells, Superoxide Anion",
author = "Hirokazu Yokoyama and Masahiko Fukuda and Yukishige Okamura and Takeshi Mizukami and Hideki Ohgo and Yoshitaka Kamegaya and Shinzo Kato and Hiromasa Ishii",
year = "1999",
month = "4",
language = "English",
volume = "23",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "4 SUPPL.",

}

TY - JOUR

T1 - Superoxide anion release into the hepatic sinusoid after an acute ethanol challenge and its attenuation by Kupffer cell depletion

AU - Yokoyama, Hirokazu

AU - Fukuda, Masahiko

AU - Okamura, Yukishige

AU - Mizukami, Takeshi

AU - Ohgo, Hideki

AU - Kamegaya, Yoshitaka

AU - Kato, Shinzo

AU - Ishii, Hiromasa

PY - 1999/4

Y1 - 1999/4

N2 - Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome e method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 ± 0.01 vs. 0.12 ± 0.02 o.d., p < 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 ± 0.002 vs. 0.008 ± 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell-depleted rats, compared with the controls (0.14 ± 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 ± 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol-induced liver injury.

AB - Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome e method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 ± 0.01 vs. 0.12 ± 0.02 o.d., p < 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 ± 0.002 vs. 0.008 ± 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell-depleted rats, compared with the controls (0.14 ± 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 ± 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol-induced liver injury.

KW - Cytochrome C

KW - Ethanol

KW - Hepatic Sinusoidal Endothelial Cell

KW - Kupffer Cells

KW - Superoxide Anion

UR - http://www.scopus.com/inward/record.url?scp=0032963739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032963739&partnerID=8YFLogxK

M3 - Article

VL - 23

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 4 SUPPL.

ER -