The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats

Background/Aims. Hepatic ischemia-reperfusion (I/R) injury is a serious concern during hepatic vascular occlusion. The objectives of this study were to assess effects of three techniques for hepatic vascular occlusion on I/R injury and to explore the underlying mechanisms. Methods. Liver cirrhotic rats had undertaken Pringle maneuver (PR), hemihepatic vascular occlusion (HH), or hepatic blood inflow occlusion without hemihepatic artery control (WH). Levels of tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), TIR-domain-containing adapter-inducing interferon-β (TRIF), and hemeoxygenase 1 (HMOX1) were assayed. Results. The histopathologic analysis displayed that liver harm was more prominent in the PR group, but similar in the HH and WH groups. The HH and WH groups responded to hepatic I/R inflammation similarly but better than the PR group. Mechanical studies suggested that TNF-α/NF-κB signaling and TLR4/TRIF transduction pathways were associated with the differential effects. In addition, the HH and WH groups had significantly higher levels of hepatic HMOX1 (P<0.05) than the PR group. Conclusions. HH and WH confer better preservation of liver function and protection than the Pringle maneuver in combating I/R injury. Upregulation of HMOX1 may lead to better protection and clinical outcomes after liver resection.

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Global proteome profiling of human livers upon ischemia/reperfusion treatment

Clinical Proteomics ◽

10.1186/s12014-020-09310-w ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Haijian Cai ◽

Shunli Qi ◽

Qi Yan ◽

Jun Ling ◽

Jian Du ◽

...

Keyword(s):

Proteomic Analysis ◽

Metabolic Pathways ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Research Direction ◽

Bioinformatic Analysis ◽

Pringle Maneuver ◽

Hepatic Ischemia ◽

Hepatic Ischemia Reperfusion

AbstractHepatic ischemia/reperfusion (I/R) injury represents a major risk factor for liver transplantation and is related to graft dysfunction and acute/chronic rejection. However, a significant part of these processes remain poorly characterized. To reveal differences in the proteome during liver I/R injury, we collected human liver biopsy samples during hepatectomy before and after the Pringle maneuver and conducted a TMT-based proteomic analysis through quantitative high-throughput mass spectrometry. We used a fold-change threshold of 1.3 and a t-test p-value < 0.05 as the criteria to identify 5,257 total quantifiable proteins. The levels of 142 proteins were increased, while the levels of 103 proteins were decreased in response to hepatic I/R treatment. Bioinformatic analysis further revealed that these differentially expressed proteins are mainly involved in multiple biological functions and enzyme-regulated metabolic pathways. Most proteins whose expression was changed are related to the defense, immune and inflammatory responses as well as lipid and steroid metabolic processes. Based on this finding, we developed a panel for targeted proteomic analysis and used the parallel reaction monitoring (PRM) method, qPCR and western blotting experiments to validate alterations in the expression of some of the identified proteins. The upregulated proteins were found to be involved in immunity and inflammatory responses, and downregulated proteins were enriched in metabolic pathways. This study therefore may provide a research direction for the design of new therapeutic strategies for hepatic ischemia/reperfusion injury.

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The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion

Journal of Experimental Medicine ◽

10.1084/jem.20042614 ◽

2005 ◽

Vol 201 (7) ◽

pp. 1135-1143 ◽

Cited By ~ 794

Author(s):

Allan Tsung ◽

Rohit Sahai ◽

Hiroyuki Tanaka ◽

Atsunori Nakao ◽

Mitchell P. Fink ◽

...

Keyword(s):

Ischemia Reperfusion ◽

High Mobility ◽

Neutralizing Antibody ◽

Nuclear Factor Κb ◽

Organ Damage ◽

Dependent Manner ◽

Nuclear Factor ◽

Hepatic Ischemia ◽

Murine Liver ◽

Hepatic Ischemia Reperfusion

High-mobility group box 1 (HMGB1) is a nuclear factor that is released extracellularly as a late mediator of lethality in sepsis as well as after necrotic, but not apoptotic, death. Here we demonstrate that in contrast to the delayed role of HMGB1 in the systemic inflammation of sepsis, HMGB1 acts as an early mediator of inflammation and organ damage in hepatic ischemia reperfusion (I/R) injury. HMGB1 levels were increased during liver I/R as early as 1 h after reperfusion and then increased in a time-dependent manner up to 24 h. Inhibition of HMGB1 activity with neutralizing antibody significantly decreased liver damage after I/R, whereas administration of recombinant HMGB1 worsened I/R injury. Treatment with neutralizing antibody was associated with less phosphorylation of c-Jun NH2-terminal kinase and higher nuclear factor–κB DNA binding in the liver after I/R. Toll-like receptor 4 (TLR4)-defective (C3H/Hej) mice exhibited less damage in the hepatic I/R model than did wild-type (C3H/HeOuj) mice. Anti-HMGB1 antibody failed to provide protection in C3H/Hej mice, but successfully reduced damage in C3H/Ouj mice. Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process.

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