Tempol, a membrane-permeable radical scavenger, reduces dinitrobenzene sulfonic acid-induced colitis.
Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of intercellular adhesion molecule 1 (ICAM-1) expression in the colon. The aim of the present study was 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 administration of dinitrobenzene sulfonic acid, the colon injury comprised of large areas of mucosal necrosis. Neutrophil infiltration (measured as increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde (an indicator of lipid peroxidation). Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed colon. Treatment of rats with tempol (15 mg/kg daily i.p.) significantly reduced the appearance of diarrhea and the loss in body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture as well as a significant reduction in the degree of both neutrophil infiltration and lipid peroxidation in the inflamed colon. Tempol also reduced the appearance of nitrotyrosine and poly (ADP-ribose) synthetase 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 radical scavengers, such as tempol, exert beneficial effects in experimental colitis and may, hence, be useful in the treatment of inflammatory bowel disease.
Cuzzocrea
S
S
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica--Policlinico Universitario Via C. Valeria-- Gazzi-98100, Messina, Italy. salvator@www.unime.it
McDonald
M C
MC
Mazzon
E
E
Dugo
L
L
Lepore
V
V
Fonti
M T
MT
Ciccolo
A
A
Terranova
M L
ML
Caputi
A P
AP
Thiemermann
C
C
D000818:Animals; D001557:Benzenesulfonates / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D002463:Cell Membrane Permeability; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013154:Spleen / Q000473:pathology; D015996:Survival Rate; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D001557:Benzenesulfonates; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; C007488:dinitrobenzenesulfonic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; C001803:tempol