2005 Abstracts: Alkaline Phosphatase Attenuates Liver and Lung Injury in a Model of Liver Ischemia-Reperfusion with Partial Hepatectomy in Rats
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Alkaline Phosphatase Attenuates Liver and Lung Injury in a Model of Liver Ischemia-Reperfusion with Partial Hepatectomy in Rats
Suzanne Q. Veen, Arlène K. Vliet, Sander Dinant, Thomas M. Gulik, Academic Medical Center, University of Amsterdam, Amsterdam, Noord-Holland, Netherlands
Introduction.
Both in liver ischemia-reperfusion (I/R) and partial hepatectomy (PHX), endotoxin (lipopolysaccharide, LPS) mediates organ damage in the liver and other organs, such as the lungs. Alkaline phosphatase dephosphorylates LPS into non-toxic monophosphate-LPS, and thus detoxifies LPS. The aim of this study was to determine the effects of BIAP on (LPS mediated) liver and lung damage, in a rat model of liver I/R with PHX. Methods. Male Wistar rats were subjected to 70% liver I/R with or without PHX of all non-ischemic lobes (30%) during the ischemic period, or to PHX only, or sham operation. Single dose of BIAP (0.5 IU/g body weight) or an equal volume of saline was given intravenously 5 min before reperfusion or. After 24 hours reperfusion rats were sacrificed for collection of blood, liver and lungs. Parameters assessed were plasma AST and ALT, wet/dry-weight ratios (measure for tissue water content), myeloperoxidase (MPO, a measure for neutrophil activation), and histopathology of both liver and lungs, to measure hepatocellular and pulmonary damage. Results. After I/R only, increased water content (wet/dry ratios) of both liver and lungs was demonstrated, which was reduced after BIAP treatment (p<0.05). Also, MPO activity and histopathology scores of liver as well as lungs were reduced after BIAP (p<0.05), but no effect on transaminase activity in plasma was observed. However, in the I/R-PHX groups, BIAP treatment reduced plasma AST and ALT compared to saline, as well as improved wet/dry ratio and histopathology scores of the liver and decreased MPO activity (all p<0.05). In the lungs after I/R-PHX, BIAP treatment reduced histopathology scores, but no effect on pulmonary water content nor on MPO activity was observed. Conclusions. In this study, administration of BIAP reduced (endotoxin mediated) liver and lung injury after liver I/R, whereas after liver I/R-PHX, BIAP attenuated hepatocellular damage as well as inflammation, and improved pulmonary histology.
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