Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion--effects of pretreatment with N-acetyl-L-cysteine and indomethacin.
BACKGROUND
Pathophysiological mechanisms and ways to intervene on intestinal barrier dysfunction following small intestinal ischaemia and prolonged reperfusion are still not fully clarified.


OBJECTIVE
To evaluate the effect of oxygen free radical and prostaglandin inhibition on intestinal barrier injury following intestinal ischaemia/reperfusion.


METHODS
Endothelial and epithelial barrier permeability was evaluated by clearance of radiolabelled albumin. Parameters included 125I-Escherichia coli uptake rate index, host reticuloendothelial system function and organ distribution, as well as protease inhibitor and proenzyme activities in rats subjected to small intestinal ischaemia for 40 minutes followed by 12 hours reperfusion (ischaemia/reperfusion), pretreated with N-acetyl-L-cysteine or indomethacin.


RESULTS
Following ischaemia/reperfusion, endothelial and epithelial permeability increased, reticuloendothelial system activation occurred and plasma protease inhibitors were consumed. N-acetyl-L-cysteine pretreatment resulted in improved endothelial and epithelial barrier integrity, a decrease in protease inhibitor consumption and less pronounced reticuloendothelial system activation. Pretreatment with indomethacin was not effective.


CONCLUSIONS
Oxygen free radicals seem to play an important role in the development of intestinal barrier impairment following ischaemia/reperfusion. N-acetyl-L-cystine may be a potential agent for preventing ischaemia/reperfusion damage.
Sun
Z
Z
Department of Surgery, Lund University Hospital, Lund, Sweden.
Lasson
A
A
Olanders
K
K
Deng
X
X
Andersson
R
R
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004727:Endothelium / Q000503:physiopathology; D004848:Epithelium / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D012157:Mononuclear Phagocyte System / Q000503:physiopathology*; D010539:Permeability / Q000187:drug effects; D011480:Protease Inhibitors / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D011480:Protease Inhibitors; D000111:Acetylcysteine; D007213:Indomethacin