Tempol, a membrane-permeable radical scavenger, reduces dinitrobenzene sulfonic acid-induced colitis

Inflammatory bowel disease is characterized by oxidative and nitrosative st ress, leukocyte infiltration, and up-regulation of intercellular adhesion m olecule 1 (ICAM-1) expression in the colon. The aim of the present study wa s to examine the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid. Rats experienced bloody diarrhea and significant loss of body weight. At 4 days after the a dministration of dinitrobenzene sulfonic acid, the colon injury comprised o f large areas of mucosal necrosis. Neutrophil infiltration (measured as inc rease in myeloperoxidase activity in the mucosa) was associated with up-reg ulation of ICAM-1 and expression of P-selectin and high levels of malondial dehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitro tyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed colon. Treatment of rats with tempol (15 mg/kg daily i.p.) signif icantly reduced the appearance of diarrhea and the loss in body weight. Thi s was associated with a remarkable amelioration of the disruption of the co lonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed;colon. Temp ol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synth etase immunoreactivity in the colon as well as the up-regulation of ICAM-1 and P-selectin. The results of this study suggest that membrane-permeable r adical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel d isease. (C) 2000 Elsevier Science B.V. All rights reserved.