Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats

Koichi Kimura, Tomoharu Yoshizumi, Shoichi Inokuchi, shinji itoh, Takashi Motomura, Yohei Mano, Takeo Toshima, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

Original languageEnglish
Pages (from-to)391-396
Number of pages6
JournalHepatology Research
Volume48
Issue number5
DOIs
Publication statusPublished - Apr 1 2018

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Thrombomodulin
Liver
Wounds and Injuries
Cell Nucleus
Serum
Alanine Transaminase
Reperfusion
Hepatocytes
Interleukin-6

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases

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Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats. / Kimura, Koichi; Yoshizumi, Tomoharu; Inokuchi, Shoichi; itoh, shinji; Motomura, Takashi; Mano, Yohei; Toshima, Takeo; Harada, Noboru; Harimoto, Norifumi; Ikegami, Toru; Soejima, Yuji; Maehara, Yoshihiko.

In: Hepatology Research, Vol. 48, No. 5, 01.04.2018, p. 391-396.

Research output: Contribution to journalArticle

Kimura, Koichi ; Yoshizumi, Tomoharu ; Inokuchi, Shoichi ; itoh, shinji ; Motomura, Takashi ; Mano, Yohei ; Toshima, Takeo ; Harada, Noboru ; Harimoto, Norifumi ; Ikegami, Toru ; Soejima, Yuji ; Maehara, Yoshihiko. / Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats. In: Hepatology Research. 2018 ; Vol. 48, No. 5. pp. 391-396.
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abstract = "Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.",
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AU - Kimura, Koichi

AU - Yoshizumi, Tomoharu

AU - Inokuchi, Shoichi

AU - itoh, shinji

AU - Motomura, Takashi

AU - Mano, Yohei

AU - Toshima, Takeo

AU - Harada, Noboru

AU - Harimoto, Norifumi

AU - Ikegami, Toru

AU - Soejima, Yuji

AU - Maehara, Yoshihiko

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

AB - Aim: Liver ischemia–reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Methods: Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. Results: In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(−) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(−) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24 h after surgery were significantly lower in the rTM(+) group than the rTM(−) group (P < 0.001). The plasma alanine aminotransferase level at 24 h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(−) group (P < 0.001). The necrotic area of the liver tissue 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(−) group (P < 0.001). Conclusions: Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

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