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Lisofylline ameliorates intestinal mucosal barrier dysfunction caused by ischemia and ischemia/reperfusion.

Abstract
In an effort to determine whether treatment with lisofylline (LSF) ameliorates intestinal barrier dysfunction in rats subjected to mesenteric ischemia and reperfusion (I/R), regional mesenteric vessels were occluded for 60 min and then unclamped for 60 min more. In Protocol 1, intravenous LSF (15 mg/kg bolus then 10 mg/kg/h) was administered 5 min before ischemia. In Protocol 2, LSF (same dose) was given 1 min before reperfusion. Controls received an equivalent volume of Ringer's lactate solution. Permeability was assessed by determining the mucosal-to-serosal clearance of fluorescein isothiocyanate-conjugated dextran (4 kDa) in everted ileal gut sacs incubated ex vivo. In Protocol 1, LSF treatment during ischemia ameliorated mucosal barrier dysfunction; mean +/- SEM clearances for the LSF and Ringer's lactate solution groups after 60 min of ischemia were 34.4+/-6.1 and 64+/-7.1 nL/min/cm2, respectively; p = .007. Clearances after reperfusion were the same in the two groups. In Protocol 2, LSF treatment just before reperfusion ameliorated barrier dysfunction measured 60 min after the restoration of blood flow; clearances for the LSF and Ringer's lactate solution groups were 23.1+/-3.8 and 40.2+/-4.5 nL/min/cm2, respectively; p = .012. Treatment with LSF did not affect intestinal levels of reduced glutathione or adenosine triphosphate or the extent of histological damage to the mucosa after I/R. Nevertheless, villus height was greater in animals treated with LSF than RLS prior to ischemia in Protocol 1 (250+/-37 and 160+/-15 microm, respectively; p = .04) and during reperfusion in Protocol 2 (170+/-21 and 82+/-7 microm, respectively; p = .002). We conclude that LSF is effective in reducing both ischemia- and I/R-induced gut barrier dysfunction, possibly due to a mechanism related to preservation of villus height.
AuthorsS Wattanasirichaigoon, M J Menconi, R L Delude, M P Fink
JournalShock (Augusta, Ga.) (Shock) Vol. 11 Issue 4 Pg. 269-75 (Apr 1999) ISSN: 1073-2322 [Print] United States
PMID10220304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Adenosine Triphosphate
  • Glutathione
  • lisofylline
  • Pentoxifylline
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Cell Membrane Permeability (drug effects)
  • Glutathione (metabolism)
  • Intestinal Mucosa (drug effects, physiopathology)
  • Intestines (blood supply, pathology)
  • Ischemia (drug therapy)
  • Male
  • Pentoxifylline (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow
  • Reperfusion Injury (drug therapy)

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