Monochloramine induces acute and protracted colitis in the rat: response to pharmacological treatment.
Monochloramine is a powerful oxidative molecule that is produced in inflammatory sites. We investigated the effect of intrarectally administered monochloramine (3.2 mg) in the rat. A single enema induced after 24 h an intense inflammatory reaction characterized by mucosal necrosis, submucosal edema, hemorrhage and colonic thickening, as well as induction of nitric oxide synthase and tumor necrosis factor and an increase in the interferon gamma/interleukin 4 ratio. The inflammatory response peaked 3-5 days after monochloramine administration and then followed a extended recovery phase. At 1 week there was substantial but incomplete mucosal repair, submucosal edema, neutrophil/macrophage infiltration and increased myeloperoxydase and alkaline phosphatase activities. Oxidative stress, as determined by malonyldialdehyde levels, was prominent only in the acute phase (3-5 days). Monochloramine colitis was amenable to pharmacological treatment with sulphasalazine or prednisolone, suggesting that it may be used as an experimental model of inflammatory bowel disease. In conclusion, monochloramine induces acute and protracted colonic inflammation in the rat. Locally produced monochloramine might contribute to the perpetuation of inflammatory bowel disease.
Ballester
Isabel
I
Department of Pharmacology, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
González
Raquel
R
Nieto
Ana
A
Zarzuelo
Antonio
A
de Medina
Fermín Sánchez
FS
D000285:Administration, Rectal; D000818:Animals; D015153:Blotting, Western; D002700:Chloramines / Q000008:administration & dosage / Q000633:toxicity*; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D017931:DNA Primers; D005260:Female; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002700:Chloramines; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C030816:chloramine