Published online before print June 14, 2004
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* Department of Gastroenterology, Hospital Clínic, Institut de Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain;
IIBB, CSIC, IDIBAPS, Barcelona, Spain; and
Tedec-Meiji Farma Laboratories, Madrid, Spain
1 Correspondence: Gastroenterology Department, Hospital Clínic, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain. E-mail: panes{at}ub.edu
Oxidant stress has been implicated in the pathogenesis of inflammatory bowel disease. Antioxidant enzymes, such as superoxide dismutase (SOD), are candidate drugs for modulating this pathogenic factor. This study was designed to determine the therapeutic value of SOD in an experimental model of colitis and to study the mechanisms underlying its effects on intestinal inflammation. For that purpose, colitic (trinitrobenzene sulfonic acid-induced) and control rats were studied. Groups of colitic animals were treated with different doses of SOD (1, 4, or 13 mg/kg/day) or vehicle, starting after induction of colitis and during 7 days. Clinical and pathological markers of colitis severity and lipid peroxidation in colonic tissue were measured. Leukocyte-endothelial cell interactions in colonic venules and expression of vascular cell adhesion molecule 1 (VCAM-1) were determined. Development of colitis was associated with a significant loss in body weight, an increase in macroscopic and microscopic damage scores, and colonic myeloperoxidase activity. Administration of SOD significantly attenuated these changes in a dose-dependent manner and reduced lipid peroxidation in colonic tissue. The increase in leukocyte rolling and adhesion in colonic venules of colitic rats were significantly reduced by administration of SOD, 13 mg/kg/day. Development of colitis was associated with a marked increase in endothelial VCAM-1 expression, which was significantly reduced by treatment with SOD. In conclusion, treatment with SOD significantly reduces peroxidation reactions in the inflamed colon and affords significant amelioration of colonic inflammatory changes in experimental colitis. This effect is related to a reduction in VCAM-1 expression and leukocyte recruitment into the inflamed intestine.
Key Words: inflammatory bowel disease • reactive oxygen species • vascular cell adhesion molecule-1
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