scholarly journals Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice

2007 ◽  
Vol 292 (5) ◽  
pp. G1385-G1395 ◽  
Author(s):  
Tadashi Hasegawa ◽  
Yoshiya Ito ◽  
Jayanthika Wijeweera ◽  
Jie Liu ◽  
Ernst Malle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Liver Blood Flow ◽  
Alanine Transaminase ◽  
Transaminase Activity ◽  
Hepatic Ischemia

Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12–24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 ± 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 ± 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ob mice during reperfusion. In contrast, sham-operated ob/ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil-induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers.

scholarly journals Mesenchymal Stem Cells Ameliorate Hepatic Ischemia/Reperfusion Injury via Inhibition of Neutrophil Recruitment

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shihui Li ◽  
Xu Zheng ◽  
Hui Li ◽  
Jun Zheng ◽  
Xiaolong Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Migration ◽  
Neutrophil Infiltration ◽  
Hepatic Ischemia ◽  
The Impact

Ischemia/reperfusion injury (IRI) remains a major problem in organ transplantation, which represents the main cause of graft dysfunction posttransplantation. Hepatic IRI is characterized by an excessive inflammatory response within the liver. Mesenchymal stem cells (MSCs) have been shown to be immunomodulatory cells and have the therapeutic action on IRI in several organs. However, the mechanism of regulatory effect of MSCs on IRI remains unclear. In the present study, we examined the impact of MSCs on hepatic inflammatory response such as neutrophil influx and liver damage in a rat model of 70% hepatic IRI. Treatment with MSCs protected rat against hepatic IRI, with significantly decreased serum levels of liver enzymes, attenuated hepatic neutrophil infiltration, reduced expression of apoptosis-associated proteins, and ameliorated liver pathological injury. MSCs also significantly enhanced the intracellular activation of p38 MAPK phosphorylation, which led to decreased expression of CXCR2 on the surface of neutrophils. In addition, MSCs significantly diminished neutrophil chemoattractant CXCL2 production by inhibiting NF-κB p65 phosphorylation in macrophages. These results demonstrate that MSCs significantly ameliorate hepatic IRI predominantly through its inhibitory effect on hepatic neutrophil migration and infiltration.

Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning

2003 ◽  
Vol 284 (1) ◽  
pp. G15-G26 ◽  
Author(s):  
Hartmut Jaeschke
Keyword(s):  
Reperfusion Injury ◽  
Liver Surgery ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Cellular Mechanisms ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Ischemia-reperfusion injury is, at least in part, responsible for the morbidity associated with liver surgery under total vascular exclusion or after liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms that contribute to various degrees in the overall injury. Some of the topics discussed in this review include cellular mechanisms of injury, formation of pro- and anti-inflammatory mediators, expression of adhesion molecules, and the role of oxidant stress during the inflammatory response. Furthermore, the roles of nitric oxide in preventing microcirculatory disturbances and as a substrate for peroxynitrite formation are reviewed. In addition, emerging mechanisms of protection by ischemic preconditioning are discussed. On the basis of current knowledge, preconditioning or pharmacological interventions that mimic these effects have the greatest potential to improve clinical outcome in liver surgery involving ischemic stress and reperfusion.

Mechanisms of hypothermic protection against ischemic liver injury in mice

2002 ◽  
Vol 282 (4) ◽  
pp. G608-G616 ◽  
Author(s):  
Atsushi Kato ◽  
Saurabh Singh ◽  
Kenneth R. McLeish ◽  
Michael J. Edwards ◽  
Alex B. Lentsch
Keyword(s):  
Transcription Factor ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dry Weight ◽  
Nuclear Factor Κb ◽  
Neutrophil Accumulation ◽  
Hepatic Ischemia

Hepatic hypothermia can safely prolong the duration of hepatic inflow occlusion during complex liver resectional surgeries. The mechanism(s) by which hypothermia protects against this form of liver ischemia-reperfusion injury are not completely understood. In this study, we sought to determine whether hypothermia protects against ischemia-reperfusion injury by altering the hepatic inflammatory response. Mice undergoing 90 min of partial hepatic ischemia followed by up to 8 h of reperfusion had their body temperatures regulated at 35–37°C (normothermic) or unregulated, in which rectal temperature dropped as low as 25°C by the end of ischemia (hypothermic). Hypothermic mice had less liver injury vs. normothermic mice, as assessed histologically, by serum transaminase levels (89% decrease), and by liver wet-to-dry weight ratios (91% decrease). Neutrophil accumulation was absent in hypothermic mice (99% reduction vs. normothermic mice). Production of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 were reduced by up to 92%. Activation of the transcription factor nuclear factor-κB was not reduced in hypothermic mice, but activation of c-Jun NH2-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 were greatly diminished. These data suggest that hypothermia suppresses the hepatic inflammatory response through selective inhibition of JNK and AP-1.

Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats

2006 ◽  
Vol 26 (6) ◽  
pp. 734-741 ◽  
Author(s):  
Matthias Behrends ◽  
Ryutaro Hirose ◽  
Natalie J. Serkova ◽  
John L. Coatney ◽  
Melanie Bedolli ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mild Hypothermia ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

scholarly journals Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response

Oncotarget ◽  
2016 ◽  
Vol 7 (19) ◽  
pp. 27711-27723 ◽  
Author(s):  
Chang Xian Li ◽  
Chung Mau Lo ◽  
Qizhou Lian ◽  
Kevin Tak-Pan Ng ◽  
Xiao Bing Liu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Activator Protein ◽  
Hepatic Ischemia Reperfusion
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