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SHR Neuro Krebs Kardio Lipid

Hasegawa, T; Ito, Y; Wijeweera, J; Liu, J; Malle, E; Farhood, A; McCuskey, RS; Jaeschke, H.
Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice.
Am J Physiol Gastrointest Liver Physiol. 2007; 292(5): G1385-G1395. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Malle Ernst

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Number of Figures: 10
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Cell Adhesion Molecules - biosynthesis
Chemokines - biosynthesis
Cytokines - biosynthesis
Fatty Liver - immunology
Inflammation - physiopathology
Liver - blood supply
Liver Circulation - physiology
Male - physiology
Mice - physiology
Mice, Inbred C57BL - physiology
Mice, Obese - physiology
Microcirculation - physiology
Neutrophils - physiology
Reperfusion Injury - immunology

Find related publications in this database (Keywords)
liver blood flow
microvascular dysfunction
heme oxygenase-1
hypochlorous acid
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