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, Yuko Kitagawa

Research output: Contribution to journalArticle

29 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 1

Keywords

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

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    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, 34(6), 573-579. https://doi.org/10.1097/SHK.0b013e3181df0433