Attenuation of epithelial injury in acute experimental colitis by immunomodulators

Higa, A.; McKnight, G. Webb; Wallace, John L.

doi:10.1016/0014-2999(93)90990-y

Cited by 32 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNB-colitis induced in experimental animals has been demonstrated to respond to drugs used in treatment of human IBD [22]. In addition, the availability of a quantitative scoring system for pathology makes TNB colitis useful for evaluating new therapeutic agents [23]. We now report that the MMP inhibitor BB-94, administered for several days (7 days) in a well-established animal model of colitis with typical histological signs of chronic inflammation produced beneficial effects and protected the colonic mucosa against tissue damage and inflammation induced by the colitis.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in Rat Experimental Colitis

Sebastiano

Mola²,

Artese³

et al. 2001

Digestion

View full text Add to dashboard Cite

Background and Aims: Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix composition playing a major role in the inflammatory response. In the present study we evaluated the ability of the MMP inhibitor Batimastat (BB-94) to modify the course of experimental colitis induced in the rat by trinitrobenzensulfonic acid (TNB). Methods: Colitis was induced in 40 rats by intracolonic administration of TNB. Animals were divided into four groups of ten rats each: group 1 received only intracolonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB+10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was administered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals were killed after seven days; segments of colon were removed and used for histological score of inflammation and myeloperoxidase (MPO) activity. Results: Rats receiving only intracolonic 0.9% saline showed no evidence of colitis. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-treated rats) exhibited a high inflammation score (12.4) and MPO activity (0.715 U/mg). Conversely, BB-94-treated rats showed, compared to the TNB group, a significantly lower inflammation score and MPO activity in a dose-dependent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.05 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 vs. TNB); group 4: inflammatory score 5.0, MPO activity 0.256 (p < 0.01 vs. TNB). Conclusions: Treatment with BB-94 has dose-dependent beneficial effects on the inflammatory alterations in rat experimental colitis. Thus, the inhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in Rat Experimental Colitis

Sebastiano

Mola²,

Artese³

et al. 2001

Digestion

View full text Add to dashboard Cite

show abstract

“…Therefore, it is speculated that an improvement on the mucosal integrity may contribute to a reduction of the intestinal inflammation [6,7].…”

Section: Introductionmentioning

confidence: 99%

Effects of dietary fiber on inflammatory bowel disease

Gálvez¹,

Rodríguez-Cabezas²,

Zarzuelo³

2005

Molecular Nutrition Food Res

205

143

View full text Add to dashboard Cite

The chronic idiopathic inflammatory bowel diseases (IBDs), namely Crohn's disease and ulcerative colitis, appear to be derived from an inappropriate reaction towards a luminal agent, most probably driven by the intestinal microflora, which upregulates the synthesis and release of different pro-inflammatory mediators, thus contributing to tissue damage that characterizes these intestinal conditions. Several studies have reported that IBD is associated with impairment in short-chain fatty acid (SCFA) production, mainly acetate, propionate, and butyrate. They are produced in the large bowel by anaerobic bacterial fermentation of undigested dietary carbohydrates and fiber polysaccharides, with butyrate being considered as the major fuel source for colonocytes. These SCFAs have been proposed to play a key role in the maintenance of colonic homeostasis. Therefore, it is reasonable to consider therapeutic approaches that increase colonic SCFA production, as it can be achieved by administration of dietary fiber to IBD patients. Unfortunately, there is quite limited documentation of efficacy of dietary fiber in properly designed trials. This review discusses the rationale, available evidence for the use of dietary fiber and its mechanisms of action in the treatment and prevention of IBDs.

show abstract

“…FK506 demonstrated to be a very potent drug in the treatment of severe cases of IBD in animal studies as well as in clinical trials (7,8,(24)(25)(26). However, the risk of distinct adverse effects after systemic absorption hinders the drug from becoming a standard therapeutic approach in the therapy of this disease pattern.…”

Section: Discussionmentioning

confidence: 99%

FK506 Microparticles Mitigate Experimental Colitis with Minor Renal Calcineurin Suppression

et al. 2005

View full text Add to dashboard Cite

show abstract

Attenuation of epithelial injury in acute experimental colitis by immunomodulators

Cited by 32 publications

References 22 publications

Beneficial Effects of Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in Rat Experimental Colitis

Beneficial Effects of Batimastat (BB-94), a Matrix Metalloproteinase Inhibitor, in Rat Experimental Colitis

Effects of dietary fiber on inflammatory bowel disease

FK506 Microparticles Mitigate Experimental Colitis with Minor Renal Calcineurin Suppression

Contact Info

Product

Resources

About