Premium
The effect of an inhibitor of matrix metalloproteinases on colonic inflammation in a trinitrobenzenesulphonic acid rat model of inflammatory bowel disease
Author(s) -
Akilah Sykes,
Ranjev Bhogal,
Christopher Brampton,
C. L. Chander,
C. J. Whelan,
Marie J. Parsons,
John Bird
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00633.x
Subject(s) - medicine , myeloperoxidase , matrix metalloproteinase inhibitor , matrix metalloproteinase , inflammation , colitis , inflammatory bowel disease , ulcerative colitis , bioavailability , tumor necrosis factor alpha , pharmacology , gastroenterology , immunology , disease
Background : Recent publications have reported that matrix metalloproteinases (MMPs) are expressed in colonic tissue taken from ulcerative colitis and Crohn’s disease patients. Aim : To evaluate the effects of a matrix metalloproteinase inhibitor, marimastat, on colonic inflammation in experimental colitis induced by trinitrobenzenesulphonic acid (TNBS)‐ethanol in the rat. Methods : Rats were dosed (by mouth) for 7 days (b.d.) with either sulphasalazine (50 mg/kg), marimastat (40 mg/kg) or vehicle. TNBS‐ethanol was administered rectally on the 4th day of dosing. On the last day of dosing, colons were removed and assessed for inflammation using myeloperoxidase activity, production of soluble TNF α (tumour necrosis factor α ), clinical score and histological assessment. In addition, the bioavailability and effect of marimastat on a range of MMPs were assessed in‐vitro . Results : In this study we have confirmed that marimastat is a broad spectrum MMPI with a bioavailability of 5%. TNBS rats dosed with sulphasalazine had a significantly lower ( P < 0.05) myeloperoxidase activity, TNF α production and a markedly lower clinical score. Similarly, rats dosed with marimastat had a significantly lower ( P < 0.05) myeloperoxidase activity and clinical score, but the TNF α production was not significantly reduced. Conclusions : Dosing rats with TNBS‐induced colitis using sulphasalazine or marimastat produced a significant reduction in tissue injury and inflammation.