Potential mechanisms responsible for zymosan-associated endothelial injury in rats.
OBJECTIVE
To assess alterations in endothelial barrier integrity and potential factors involved in zymosan-associated endothelial injury.


METHODS
Experimental study.


METHODS
University hospital, Sweden.


METHODS
42 adult male Sprague-Dawley rats.


METHODS
One hour before an intraperitoneal injection of paraffin or zymosan (0.25 mg/g body weight), 1.0 ml of a solution of saline, N-acetyl-L-cysteine, dimethyl sulphoxide, indomethacin, verapamil, or allopurinol was given intravenously.


METHODS
Measurement of tissue water content, tissue intravascular plasma volume, interstitial fluid volume, and extravascular 125I-labelled human serum albumin distribution as well as plasma concentrations of albumin, alpha1-macroglobulin, alpha2-antiplasmin, and antithrombin III, 24 hours after the intraperitoneal injection.


RESULTS
Endothelial permeability significantly increased in abdominal organs and the gastrointestinal tract, and plasma antiplasmin concentrations decreased. Pretreatment with N-acetyl-L-cysteine, dimethyl sulphoxide, or indomethacin protected against zymosan-induced endothelial barrier injury and the decline in protease inhibitors in plasma to varying degrees, while pretreatment with verapamil or allopurinol had a limited effect.


CONCLUSIONS
Oxygen free radicals, prostaglandin, and proteases may have roles in the pathogenesis of zymosan-induced endothelial barrier injuries, implying that several mediators probably are interacting.
Deng
X
X
Department of Surgery, Lund University Hospital, Sweden.
Lasson
A
A
Wang
X
X
Haraldsen
P
P
Andersson
R
R
D000818:Animals; D001777:Blood Coagulation; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D004727:Endothelium / Q000473:pathology*; D005069:Evaluation Studies as Topic; D005342:Fibrinolysis; D005609:Free Radicals / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015054:Zymosan / Q000493:pharmacokinetics* / Q000494:pharmacology
D005609:Free Radicals; D011453:Prostaglandins; D015054:Zymosan; D002118:Calcium