Dec 6, 2001

Protective effects of M40403, a superoxide dismutase mimetic, in a rodent model of colitis

European Journal of Pharmacology
S CuzzocreaD Salvemini

Abstract

Inflammatory bowel disease is characterised 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 M40403, a superoxide dismutase mimetic, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid (TNBS). Rats experienced bloody diarrhoea and significant loss of body weight. At 4 days after TNBS administration, the colon damage was characterised by areas of mucosal necrosis. Neutrophil infiltration (indicated by myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1 and expression of P-selectin and high levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) synthetase showed an intense staining in the inflamed colon. Treatment with M40403 (5 mg/kg daily i.p.) significantly reduced the appearance of diarrhoea and the loss of body weight. This was associated with a remarkable amelioration of the disruption of the colonic architecture as well as a significant reduction of colonic myeloperoxidase activity and malondialdehyde levels. M40403 also r...Continue Reading

  • References49
  • Citations35

References

  • References49
  • Citations35

Citations

Mentioned in this Paper

SELP gene
Manganese
Mpo
Taenia Coli
Immunohistochemistry
Immunoreactivity
Mucositis
Organometallic Compounds
Weighing Patient
Imisopasem manganese

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