Can reperfusion injury of the liver be prevented? Trying to improve on a good thing

Olthoff, Kim M.

doi:10.1034/j.1399-3046.2001.00047.x

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…The possible consequences of IRI include both primary severe liver dysfunction and secondary multi-organ system failure that eventually lead to mortality [2][3][4]. The mechanisms underlying hepatic IRI are complex but are known to involve leukocyte accumulation and activation (neutrophils, Kupffer cells, and T cells), leading to the formation of reactive oxygen species (ROS), secretion of pro-inflammatory cytokines/chemokines, complement activation, and vascular cell adhesion molecule activation [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia–Reperfusion Injury

et al. 2013

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Background Sivelestat sodium hydrate (sivelestat) is a specific neutrophil elastase inhibitor that is effective in treating acute lung injury associated with systemic inflammatory response syndrome. As such, it may be useful in treating hepatic ischemia-reperfusion injury (IRI), a condition in which neutrophils transmigrate into the interstitium, leading to release of neutrophil elastase from neutrophils and consequent damage to the affected tissue, particularly in cases of hepatic failure after liver transplantation or massive liver resection. Aims The purpose of this study was to examine whether treatment with sivelestat inhibits neutrophil adhesion and migration to the vessel wall and suppresses hepatic IRI. Methods Whether and, if so, the extent to which sivelestat suppresses the adhesion and migration of neutrophils and reduces liver damage in hepatic IRI was examined in a human umbilical vein endothelial cell (HUVEC) model and a rat hepatic IRI model. Results In the HUVEC model, the extent of the adhesion and migration of neutrophils stimulated by platelet-activating factor were found to be dose-dependently inhibited by sivelestat treatment (p \ 0.05). In the rat model, serum liver enzyme levels were significantly lower at 12 h after reperfusion, and the number of neutrophils that had migrated to extravascular sites was significantly less in the treatment group compared to the control group (p \ 0.05). Conclusion Sivelestat inhibits the adhesion and migration of neutrophils to vascular endothelium in hepatic IRI, thereby suppressing liver injury.

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Section: Introductionmentioning

confidence: 99%

Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia–Reperfusion Injury

et al. 2013

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“…[1][2][3] It is a major cause of morbidity and mortality after liver surgery. Currently, the treatments of hepatic I/R injury is merely supportive care.…”

mentioning

confidence: 99%

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Sun

Yuan

et al. 2014

Biological & Pharmaceutical Bulletin

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Cryptotanshinone (CT), isolated from the dried roots of Salvia militorrhiza, has been reported to have protective effects on myocardial and cerebral ischemia/reperfusion (I/R) injury both in vitro and in vivo. However, its effects and underlying mechanism on hepatic I/R injury remain unclear. To investigate its effects on hepatic I/R injury, thirty male Sprague-Dawley rats were randomized into 3 groups: a sham group, a vehicle-treated hepatic I/R group and a CT-treated (50 mg/kg) group. The hepatic I/R and CT-treated groups were subjected to 60 min of normothermic ischemia of the left lateral lobe of the liver, followed by 4 h of reperfusion. The animals were then sacrificed to collect the serum and the left liver lobe for assay. Hepatic function was protected, as evidenced by significantly reduced alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) levels in the CT-treated group as compared with I/R group. The terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) demonstrated significantly decreased apoptosis in the CT-administration animals. Western blotting demonstrated upregulation of the proapoptotic protein Bcl-2, as well as decreased levels of the activated form of caspase-3 and the cleaved form of its substrate, poly(ADP-ribose) polymerase (PARP) in the CT-treated group compared with those of the I/R group. In addition, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) was inhibited by CT. Our data suggest that CT attenuates hepatic I/R injury by inhibiting the intrinsic pathway of apoptosis, mediated partly through the inhibition of JNK and p38 MAPK phosporylation.

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“…Hepatic IR injury is an important problem in clinical conditions such as liver surgery for tumor excision, transplantation, trauma and liver failure accompanying hemorrhagic shock [26,27]. Blood flow needs to be cut off partially or completely during liver surgery [28].…”

Section: Discussionmentioning

confidence: 99%

Effects of nitrite on hepatic ischemia-reperfusion injury

Ciftci¹,

Yalovac²,

Hekimoğlu³

et al. 2012

Turk J Bioch

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Aim: Hepatic ischemia-reperfusion (IR) injury is a major complication associated with liver transplantation and surgery. The aim of this study is to investigate the cytoprotective effects of nitrite on hepatic IR injury. Methods: Groups were arranged as follows: control, sham, IR protocol (45 minutes ischemia, 5 hours reperfusion) and study groups administered with 4 different concentrations of sodium nitrite given 12 and 24 hours prior to protocol. After IR protocol, serum transaminase and lactate dehydrogenase (LDH) enzyme activities were determined as quantitative indices of liver damage. Malondialdehyde (MDA) levels, glutathione levels and antioxidant enzyme activities were determined in liver tissues of all study groups. Additionally inflammatory and tissue remodeling processes were investigated. Histological evaluations were also performed. Results: Serum transaminase and LDH activities were found to be increased in IR group compared to control group. Glutathione content and ratio of reduced glutathione to oxidized glutathione were found to be significantly decreased; oxidized glutathione and MDA content significantly increased in the IR group. All antioxidant enzyme activities were found to be lowered in IR group. TNF-a, IL-1b, IL-6, IL-8, IL-12, MMP-2 and MMP-9 levels were significantly increased in IR group compared to control group. In all nitrite administered groups, all parameters which were found to be changed with IR protocol were decreased to control levels depending on the concentration of nitrite. Total histological damage score at light microscope level was significantly higher in IR group. Nitrite improved histological damage scores by receiving similar scores with the control group. Conclusion: Based on findings, nitrite administration was found to have cytoprotective effects on hepatic IR injury.

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Can reperfusion injury of the liver be prevented? Trying to improve on a good thing

Cited by 21 publications

References 25 publications

Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia–Reperfusion Injury

Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia–Reperfusion Injury

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Effects of nitrite on hepatic ischemia-reperfusion injury

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