Protective effect of high-mobility group box 1 blockade on acute liver failure in rats

Kiminori Takano, Masahiro Shinoda, Minoru Tanabe, Taku Miyasho, Shingo Yamada, Shigeshi Ono, Yohei Masugi, Koichi Suda, Koichi Fukunaga, Tetsu Hayashida, Taizo Hibi, Hideaki Obara, Hiroya Takeuchi, Shigeyuki Kawachi, Kazufumi Kawasako, Minoru Okamoto, Hiroshi Yokota, Ikuro Maruyama, Yuukou Kitagawa

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. d-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the d-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of d-galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury.

Original languageEnglish
Pages (from-to)573-579
Number of pages7
JournalShock
Volume34
Issue number6
DOIs
Publication statusPublished - 2010 Dec

Fingerprint

Acute Liver Failure
Liver
Galactosamine
Antibodies
Injections
Veins
Staining and Labeling
Wounds and Injuries
Endotoxins
Sprague Dawley Rats
Monocytes
Shock
Cytokines
Enzymes
Pharmaceutical Preparations

Keywords

  • Acute liver failure
  • antibody
  • high-mobility group box 1
  • necrosis
  • rat model

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. / Takano, Kiminori; Shinoda, Masahiro; Tanabe, Minoru; Miyasho, Taku; Yamada, Shingo; Ono, Shigeshi; Masugi, Yohei; Suda, Koichi; Fukunaga, Koichi; Hayashida, Tetsu; Hibi, Taizo; Obara, Hideaki; Takeuchi, Hiroya; Kawachi, Shigeyuki; Kawasako, Kazufumi; Okamoto, Minoru; Yokota, Hiroshi; Maruyama, Ikuro; Kitagawa, Yuukou.

In: Shock, Vol. 34, No. 6, 12.2010, p. 573-579.

Research output: Contribution to journalArticle

Takano, K, Shinoda, M, Tanabe, M, Miyasho, T, Yamada, S, Ono, S, Masugi, Y, Suda, K, Fukunaga, K, Hayashida, T, Hibi, T, Obara, H, Takeuchi, H, Kawachi, S, Kawasako, K, Okamoto, M, Yokota, H, Maruyama, I & Kitagawa, Y 2010, 'Protective effect of high-mobility group box 1 blockade on acute liver failure in rats', Shock, vol. 34, no. 6, pp. 573-579. https://doi.org/10.1097/SHK.0b013e3181df0433
Takano, Kiminori ; Shinoda, Masahiro ; Tanabe, Minoru ; Miyasho, Taku ; Yamada, Shingo ; Ono, Shigeshi ; Masugi, Yohei ; Suda, Koichi ; Fukunaga, Koichi ; Hayashida, Tetsu ; Hibi, Taizo ; Obara, Hideaki ; Takeuchi, Hiroya ; Kawachi, Shigeyuki ; Kawasako, Kazufumi ; Okamoto, Minoru ; Yokota, Hiroshi ; Maruyama, Ikuro ; Kitagawa, Yuukou. / Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. In: Shock. 2010 ; Vol. 34, No. 6. pp. 573-579.
@article{da6e06519a0d4e0fbba78cfdac9b4f90,
title = "Protective effect of high-mobility group box 1 blockade on acute liver failure in rats",
abstract = "High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. d-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the d-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of d-galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury.",
keywords = "Acute liver failure, antibody, high-mobility group box 1, necrosis, rat model",
author = "Kiminori Takano and Masahiro Shinoda and Minoru Tanabe and Taku Miyasho and Shingo Yamada and Shigeshi Ono and Yohei Masugi and Koichi Suda and Koichi Fukunaga and Tetsu Hayashida and Taizo Hibi and Hideaki Obara and Hiroya Takeuchi and Shigeyuki Kawachi and Kazufumi Kawasako and Minoru Okamoto and Hiroshi Yokota and Ikuro Maruyama and Yuukou Kitagawa",
year = "2010",
month = "12",
doi = "10.1097/SHK.0b013e3181df0433",
language = "English",
volume = "34",
pages = "573--579",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Protective effect of high-mobility group box 1 blockade on acute liver failure in rats

AU - Takano, Kiminori

AU - Shinoda, Masahiro

AU - Tanabe, Minoru

AU - Miyasho, Taku

AU - Yamada, Shingo

AU - Ono, Shigeshi

AU - Masugi, Yohei

AU - Suda, Koichi

AU - Fukunaga, Koichi

AU - Hayashida, Tetsu

AU - Hibi, Taizo

AU - Obara, Hideaki

AU - Takeuchi, Hiroya

AU - Kawachi, Shigeyuki

AU - Kawasako, Kazufumi

AU - Okamoto, Minoru

AU - Yokota, Hiroshi

AU - Maruyama, Ikuro

AU - Kitagawa, Yuukou

PY - 2010/12

Y1 - 2010/12

N2 - High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. d-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the d-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of d-galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury.

AB - High-mobility group box 1 (HMGB1) is a monocyte-derived inflammatory mediator that is released in some conditions including shock, tissue injury, and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a drug-induced rat acute liver failure (ALF) model and investigated the effect of HMGB1 blockade on ALF. Adult male Sprague-Dawley rats, weighing 250 to 300 g, were used for this study. d-galactosamine was injected into the penile vein to induce ALF. To determine HMGB1 levels, plasma and hepatic tissue samples were serially collected after the d-galactosamine injection. To test the effect of HMGB1 blockade, anti-HMGB1 polyclonal antibodies or control antibodies were injected into the penile vein right after injection of d-galactosamine. Levels of HMGB1 were increased in plasma and decreased in hepatic tissue after induction of ALF. Immunohistochemical examination for HMGB1 showed that liver from animals with ALF had little staining, whereas normal liver had strong staining in the nuclei. Injection of anti-HMGB1 antibodies resulted in significant suppression of plasma HMGB1 and hepatic enzymes, marked suppression of plasma inflammatory cytokines, marked improvement of histological findings, and significant improvement of survival. The decrease of hepatic HMGB1 was also significantly suppressed in the group injected with anti-HMGB1 antibodies. The present study suggests that in ALF, the liver may release HMGB1 into the plasma, and that neutralizing the released HMGB1 has a protective effect against injury.

KW - Acute liver failure

KW - antibody

KW - high-mobility group box 1

KW - necrosis

KW - rat model

UR - http://www.scopus.com/inward/record.url?scp=78649535273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649535273&partnerID=8YFLogxK

U2 - 10.1097/SHK.0b013e3181df0433

DO - 10.1097/SHK.0b013e3181df0433

M3 - Article

VL - 34

SP - 573

EP - 579

JO - Shock

JF - Shock

SN - 1073-2322

IS - 6

ER -