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; Kawa, Shigeyuki; Kawasako, Kazufumi; Okamoto, Minoru; Yokota, Hiroshi; Maruyama, Ikuro; Kitagawa, Yuko

doi:10.1097/shk.0b013e3181df0433

Cited by 31 publications

(33 citation statements)

References 28 publications

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“…Some of our past studies have suspected the involvement of inflammatory cytokines in the pathophysiology of ALF [24,25,26]. In one of our recent studies focusing on HMGB1, we reported that the levels of HMGB1 were increased in plasma and decreased in hepatic tissue in a drug-induced ALF rat model, and that blockade of HMGB1 resulted in improvement of various parameters [11]. As an extension of our study in rats, the present study investigated the plasma levels of HMGB1 in patients with various forms of liver disease, including ALF, and assessed HMGB1 levels in hepatic tissue from ALF patients.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent investigations using animal models revealed that HMGB1 is a key mediator in various pathological conditions, such as sepsis, organ injury and endotoxin-induced lethality [4,5,6,7,8,9,10,11,12,13]. In recent investigations, increased levels of circulating HMGB1 and overexpression of HMGB1 mRNA have been identified in patients with various types of medical conditions [14,15,16,17,18,19,20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Increased Plasma Levels of High Mobility Group Box 1 in Patients with Acute Liver Failure

Oshima¹,

Shinoda²,

Tanabe³

et al. 2012

Eur Surg Res

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Background: High-mobility group box 1 (HMGB1) is a monocyte-derived late-acting inflammatory mediator, which is released in conditions such as shock, tissue injury and endotoxin-induced lethality. In this study, we determined the plasma and hepatic tissue levels of HMGB1 in patients with acute liver failure (ALF). Patients and Methods: We determined the plasma levels of HMGB1 and aspartate aminotransferase (AST) in 7 healthy volunteers (HVs), 40 patients with liver cirrhosis (LC), 37 patients with chronic hepatitis (CH), 18 patients with severe acute hepatitis (AH), and 14 patients with fulminant hepatitis (FH). The 14 patients with FH were divided into two subgroups depending upon the history of plasma exchange (PE) before their plasma sample collection. The hepatic levels of HMGB1 were measured in tissue samples from 3 patients with FH who underwent living-donor liver transplantation and from 3 healthy living donors. Hepatic tissue samples were also subjected to immunohistochemical examination for HMGB1. Results: The plasma levels of HMGB1 (ng/ml) were higher in patients with liver diseases, especially in FH patients with no history of PE, than in HVs (0.3 ± 0.3 in HVs, 4.0 ± 2.0 in LC, 5.2 ± 2.6 in CH, 8.6 ± 4.8 in severe AH, 7.8 ± 2.7 in FH with a history of PE, and 12.5 ± 2.6 in FH with no history of PE, p < 0.05 in each comparison). There was a strong and statistically significant relationship between the mean plasma HMGB1 level and the logarithm of the mean AST level (R = 0.900, p < 0.05). The hepatic tissue levels of HMGB1 (ng/mg tissue protein) were lower in patients with FH than in healthy donors (539 ± 116 in FH vs. 874 ± 81 in healthy donors, p < 0.05). Immunohistochemical staining for HMGB1 was strong and clear in the nuclei of hepatocytes in liver sections from healthy donors, but little staining in either nuclei or cytoplasm was evident in specimens from patients with FH. Conclusion: We confirmed that plasma HMGB1 levels were increased in patients with ALF. Based on a comparison between HMGB1 contents in normal and ALF livers, it is very likely that HMGB1 is released from injured liver tissue.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased Plasma Levels of High Mobility Group Box 1 in Patients with Acute Liver Failure

Oshima¹,

Shinoda²,

Tanabe³

et al. 2012

Eur Surg Res

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“…HMGB1 has recently been identified as an important mediator of various kinds of acute and chronic inflammation [2,3,4,5,6,7,8,9,10]. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

“…A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. Based on our previous experiments, various diseases including ALF, sepsis, small intestine ischemia-reperfusion, and liver ischemia-reperfusion could benefit from treatment to remove HMGB1 [8,9,10,11,12]. We have previously shown that a column containing cellulofine sulfate beads adsorbed HMGB1 in a rat sepsis model [16].…”

Section: Discussionmentioning

confidence: 99%

“…In animal models of shock, tissue injury, and endotoxin-induced lethality, HMGB1 is released from necrotic tissues and causes systemic inflammation [2,3,4,5,6,7,8]. In our previous study, we demonstrated that: (1) plasma HMGB1 levels were increased in rat models of acute liver failure (ALF), sepsis, small intestine ischemia-reperfusion, and liver ischemia-reperfusion, and (2) HMGB1 blockade by the injection of anti-HMGB1 polyclonal antibodies resulted in improvement of various parameters in those models [8,9,10]. We also showed that plasma HMGB1 levels are elevated in patients with ALF and patients after esophagectomy [11,12].…”

Section: Introductionmentioning

confidence: 99%

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Hemoadsorption of High-Mobility Group Box Chromosomal Protein 1 Using a Column for Large Animals

Nishiyama

Shinoda²,

Tanabe

et al. 2013

Eur Surg Res

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Background: High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from thesystemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases. Materials and Methods: In this study, we produced a new adsorbent material by chemicallytreating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure. Results: The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newlydeveloped column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion). Conclusion: These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.

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High‐Mobility Group Box‐1 and Liver Disease

Gaskell

Nieto

2018

Hepatology Communications

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High‐mobility group box‐1 (HMGB1) is a ubiquitous protein. While initially thought to be simply an architectural protein due to its DNA‐binding ability, evidence from the last decade suggests that HMGB1 is a key protein participating in the pathogenesis of acute liver injury and chronic liver disease. When it is passively released or actively secreted after injury, HMGB1 acts as a damage‐associated molecular pattern that communicates injury and inflammation to neighboring cells by the receptor for advanced glycation end products or toll‐like receptor 4, among others. In the setting of acute liver injury, HMGB1 participates in ischemia/reperfusion, sepsis, and drug‐induced liver injury. In the context of chronic liver disease, it has been implicated in alcoholic liver disease, liver fibrosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma. Recently, specific posttranslational modifications have been identified that could condition the effects of the protein in the liver. Here, we provide a detailed review of how HMGB1 signaling participates in acute liver injury and chronic liver disease.

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Protective Effect of High-Mobility Group Box 1 Blockade on Acute Liver Failure in Rats

Cited by 31 publications

References 28 publications

Increased Plasma Levels of High Mobility Group Box 1 in Patients with Acute Liver Failure

Increased Plasma Levels of High Mobility Group Box 1 in Patients with Acute Liver Failure

Hemoadsorption of High-Mobility Group Box Chromosomal Protein 1 Using a Column for Large Animals

High‐Mobility Group Box‐1 and Liver Disease

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