Ischemia/reperfusion injury in the rat colon.
This study investigated metabolic and biochemical consequences of colonic ischemia/reperfusion (I/R) in the rat and evaluated whether antioxidants prevent I/R-induced functional damage in the rat colon. The surgical preparation involved a 10 cm segment of the colon and occlusion of the superior mesenteric artery (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the superior mesenteric vein (SMV) was collected to measure blood gases, lactic acid (LA) and arachidonic acid (AA) metabolites. Tissue xanthine oxidase (XO) and thiobarbituric acid (TBA) derivatives were measured before and after reperfusion. In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TBA was measured. After ischemia, the colon displayed a metabolic shift from aerobic to anaerobic course by increasing lactic acid production in the colon (183% increase in SMV lactate level compared 87% in the SMA; p < 0.03). After 10 minutes of reperfusion, circulating 6-keto-prostaglandin F1 alpha increased by 3.85 fold (p < 0.001) and thromboxane B2 increased by 2 to 3 fold. An Ischemia time longer than 60 minutes was required to cause changes in tissue XO levels. Tissue TBA levels showed a good dose response corresponding with I/R time. I/R (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and mucosal permeability, respectively. MDL 73404 and 5-aminosalicylic acid significantly inhibited the vascular permeability and decreased LA, AA, XO and TBA. These observations provide the first direct experimental evidence for I/R-induced damage in the colon and some of its effects can be reversed by conventional and novel antioxidants.
Murthy
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S
Department of Medicine, Krancer Center for Inflammatory Bowel Disease Research, Cincinnati, Ohio, USA.
Hui-Qi
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Q
Sakai
T
T
Depace
D E
DE
Fondacaro
J D
JD
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000332:Aerobiosis; D000636:Aminosalicylic Acids / Q000494:pharmacology; D000693:Anaerobiosis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D003106:Colon / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D019804:Mesalamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D000636:Aminosalicylic Acids; D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; C067190:MDL 73404; D014810:Vitamin E; D016718:Arachidonic Acid; D019344:Lactic Acid; D019804:Mesalamine; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D014969:Xanthine Oxidase; D005978:Glutathione