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, Yuko
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.
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
C2 - 20351624
AN - SCOPUS:78649535273
SN - 1073-2322
VL - 34
SP - 573
EP - 579
JO - Shock
JF - Shock
IS - 6
ER -