Abstract
Lisofylline (LSF) blocks synthesis of phosphatidic acid, which is a second messenger for several pro-inflammatory stimuli. We hypothesized that intestinal mucosaI ischemia/reperfusion injury might he mediated via phosphatidic acid signaling and that might he ameliorated by treatment with LSF. Ischemia was induced in the distal ileum of Sprague-Dawley rats (250-350 grams) by occluding the regional mesenteric vessels for 60 min, followed by 60 min of reperfusion. Animals were randomized to receive i.v. LSF (15 mg/kg bolus + 10 mg/kg/hr), or an equivalent volume of Ringer's lactate solution (control). An everted gut sac technique was used to assess ileal mucosal permeability to fluorescently-labeled dextran (M.W.=4,000 Daltons), expressed as an apparent clearance(AC). Levels of reduced glutathione (GSH) were determined as a measure of oxidant stress. GSH was measured spectrophotometrically after oxidation with 5-5'-dithiobis (2-nitrobenzoic acid). No significant difference in maximal blood flow of reperfused guts was observed between the LSF-treated and control groups.
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