Alkaline phosphatase reduces hepatic and pulmonary injury in liver ischaemia -- reperfusion combined with partial resection.
BACKGROUND
Lipopolysaccharides mediate inflammation in liver ischaemia-reperfusion (I/R) and partial liver resection (PHX). Bovine intestinal alkaline phosphatase (BIAP) detoxifies lipopolysaccharides by dephosphorylation and reduces inflammation in models of sepsis. This study examined the protective effects of BIAP administration in models of partial (70 per cent) liver I/R with or without partial resection of all non-ischaemic lobes during ischaemia (30 per cent).


METHODS
Male Wistar rats were divided into six groups: I/R + BIAP, I/R + saline, I/R + PHX + BIAP and I/R + PHX + saline, PHX only or sham laparotomy only. A single dose of BIAP (0.5 units/g) or vehicle (saline) was administered 5 min before reperfusion. Inflammatory response, and hepatic and pulmonary injury were assessed during 24 h of reperfusion.


RESULTS
I/R, with or without PHX, increased all markers of inflammation, and hepatic and pulmonary damage (P < 0.050 versus sham operation). I/R + PHX significantly increased release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and hepatic neutrophil influx compared with I/R only (P < 0.050). BIAP treatment decreased hepatic wet/dry ratios, neutrophil influx and histopathological damage after I/R with or without PHX (P < 0.050), and also AST, ALT and interleukin (IL)-6 production after I/R + PHX (P < 0.050). BIAP treatment reduced the neutrophil influx after I/R, and pulmonary histopathological injury was decreased after I/R with or without PHX.


CONCLUSIONS
BIAP attenuates hepatic and pulmonary injury after partial liver I/R and PHX.
van Veen
S Q
SQ
Department of Surgery (Surgical Laboratory), Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Dinant
S
S
van Vliet
A K
AK
van Gulik
T M
TM
D000469:Alkaline Phosphatase / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D007511:Ischemia / Q000188:drug therapy*; D008026:Ligation / Q000379:methods; D008099:Liver / Q000098:blood supply* / Q000601:surgery; D008103:Liver Cirrhosis / Q000473:pathology; D008168:Lung / Q000098:blood supply*; D008297:Male; D011014:Pneumonia / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D016207:Cytokines; D000469:Alkaline Phosphatase