Protection against severe intestinal ischemia/reperfusion injury in rats by intravenous resveratrol.
BACKGROUND
Repetitive enteral or intraperitoneal administration of resveratrol at high doses has recently been found to protect the small intestine against acute ischemia/reperfusion (I/R) injury. In the present work, the protective potential of solvent-free continuous intravenous infusions of small amounts of resveratrol was studied in a model of severe intestinal I/R injury.


METHODS
Mesenteric ischemia was induced in male Wistar rats (six animals/group) by superior mesenteric artery occlusion (SMAO, 90 min) and reperfusion (120 min) by reopening of the microvascular clamp. Resveratrol (0.056 or 0.28 mg/kg) was continuously perfused into the jugular vein (0.014 or 0.07 mg/kg × h) starting 30 min before SMAO; an SMAO control group and sham groups (no SMAO) receiving either 0.9% NaCl solution or resveratrol (0.28 mg/kg) were included. During the experimental procedure, isotonic saline was given at a systolic blood pressure below 90 mmHg, and several parameters including those of biomonitoring and blood gas analysis were measured. Small intestine injury was assessed macroscopically, from released plasma enzyme activities, from the tissue contents of thiobarbituric acid-reactive substances and hemoglobin, from the tissue myeloperoxidase activity, and histopathologically.


RESULTS
Resveratrol at only 0.056 mg/kg significantly decreased the macroscopic damage score, the tissue myeloperoxidase activity, the hemoglobin content, the histopathologic score, and the plasma glutamate-pyruvate transaminase activity, but it did not improve the systemic and metabolic parameters. Instead, during reperfusion, significantly higher volumes of saline were administered to animals receiving the polyphenol, although resveratrol did not significantly affect any parameters in sham-operated animals.


CONCLUSIONS
Low doses of intravenously administered resveratrol considerably protected the rat small intestine against severe I/R injury, despite some adverse effects on blood pressure under these conditions.
Petrat
Frank
F
Institut für Physiologische Chemie, Universitätsklinikum, Universität Duisburg-Essen, Hufelandstr. 55, D-45122 Essen, Germany. frank.petrat@uni-duisburg-essen.de
de Groot
Herbert
H
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007421:Intestine, Small / Q000098:blood supply* / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D000077185:Resveratrol; D012720:Severity of Illness Index; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D013267:Stilbenes; D009195:Peroxidase; D000077185:Resveratrol